%PDF-1.6
%
1 0 obj
<>
endobj
2 0 obj
<>stream
Laura Ceballos, Alejandro Krolewiecki, Marisa Juárez, Laura Moreno, Fabian Schaer, Luis I. Alvarez, Rubén Cimino, Judd Walson, Carlos E. Lanusse
Assessment of serum pharmacokinetics and urinary excretion of albendazole and its metabolites in human volunteers
www.plosntds.org
www.plosntds.org
endstream
endobj
3 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 12 0 R/Annots 13 0 R/Contents 14 0 R/TrimBox[0 0 612 792]>>
endobj
13 0 obj
[15 0 R 16 0 R 17 0 R 18 0 R 19 0 R 20 0 R 21 0 R 22 0 R 23 0 R]
endobj
15 0 obj
<>/Border[0 0 0]/A 24 0 R>>
endobj
24 0 obj
<>
endobj
16 0 obj
<>/Border[0 0 0]/Dest(Rpntd.0005945.ref001)>>
endobj
17 0 obj
<>/Border[0 0 0]/Dest(Rpntd.0005945.ref002)>>
endobj
18 0 obj
<>/Border[0 0 0]/Dest(Rpntd.0005945.ref003)>>
endobj
19 0 obj
<>/Border[0 0 0]/Dest(Rpntd.0005945.ref001)>>
endobj
20 0 obj
<>/Border[0 0 0]/Dest(Rpntd.0005945.ref004)>>
endobj
21 0 obj
<>/Border[0 0 0]/Dest(Rpntd.0005945.ref005)>>
endobj
22 0 obj
<>/Border[0 0 0]/Dest(Rpntd.0005945.ref006)>>
endobj
23 0 obj
<>/Border[0 0 0]/A 25 0 R>>
endobj
25 0 obj
<>
endobj
14 0 obj
[26 0 R 27 0 R 28 0 R 29 0 R 30 0 R 31 0 R 32 0 R 33 0 R]
endobj
26 0 obj
<>stream
q
0.955 g
0 w
199.9998 610.6144 m
575.9997 610.6144 l
575.9997 358.615 l
199.9998 358.615 l
f*
0.45 0.36 0.35 0.01 k
575.9997 635.6143 m
199.9998 635.6143 l
199.9998 636.1143 l
575.9997 636.1143 l
f*
0.83 0.64 0.02 0 k
272.9197 648.0567 m
334.0346 648.0567 l
h
f*
285.4488 289.9276 m
290.211 289.9276 l
h
f*
203.4142 237.9402 m
208.1764 237.9402 l
h
f*
253.9843 224.9008 m
258.6898 224.9008 l
h
f*
523.3323 211.9181 m
528.0945 211.9181 l
h
f*
532.5732 211.9181 m
537.3354 211.9181 l
h
f*
226.2614 133.9087 m
231.0236 133.9087 l
h
f*
449.9717 107.9433 m
454.7339 107.9433 l
h
f*
0 g
1 j
1 J
9.5 0 0 9.5 200.0125 707.7543 cm
BT
/F0 1 Tf
1 TL
-0.0042 Tc
0 0 Td
(developing)Tj
4.9889 0 Td
(a)Tj
0.7639 0 Td
(urine)Tj
2.4109 0 Td
(based)Tj
2.9122 0 Td
(method)Tj
3.5209 0 Td
(to)Tj
1.0503 0 Td
(assess)Tj
3.3002 0 Td
(compliance)Tj
5.2217 0 Td
(to)Tj
1.0443 0 Td
(ABZ)Tj
2.1603 0 Td
(treatment.)Tj
4.6846 0 Td
(Such)Tj
2.4766 0 Td
(an)Tj
1.3129 0 Td
(assay)Tj
-35.8477 -1.474 Td
(may)Tj
2.0946 0 Td
(be)Tj
1.3188 0 Td
(useful)Tj
2.8526 0 Td
(to)Tj
1.0443 0 Td
(optimize)Tj
3.9029 0 Td
(ABZ)Tj
2.1603 0 Td
(use)Tj
1.8141 0 Td
(in)Tj
0.9787 0 Td
(human)Tj
3.2464 0 Td
(patients.)Tj
ET
Q
q
1 j
1 J
0 w
11.4998 0 0 11.4998 200.0125 666.1417 cm
BT
/F2 1 Tf
1 TL
-0.0035 Tc
0 0 Td
(Trial)Tj
2.317 0 Td
(registration)Tj
ET
Q
q
1 j
1 J
0 w
9.5 0 0 9.5 200.0125 649.1338 cm
BT
/F0 1 Tf
1 TL
-0.0042 Tc
0 0 Td
(ClinicalTrials.gov)Tj
0.83 0.64 0.02 0 k
7.6744 0 Td
(NCT03192449)Tj
0 g
(.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 209.9905 592.611 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Author)Tj
3.137 0 Td
(summary)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 209.9905 574.6393 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(The)Tj
1.7858 0 Td
(soil-transmitted-helminths)Tj
10.97 0 Td
(\(STH\))Tj
2.7496 0 Td
(infections)Tj
4.1555 0 Td
(are)Tj
1.4457 0 Td
(produced)Tj
4.0478 0 Td
(by)Tj
1.1849 0 Td
(four)Tj
1.9106 0 Td
(species)Tj
2.999 0 Td
(of)Tj
1.0148 0 Td
(para-)Tj
-32.2637 -1.3039 Td
(sites:)Tj
/F10 1 Tf
2.1543 0 Td
[()10()-3()7()16()-9()-4()]TJ
3.0217 0 Td
[()12()12( )17(\n)11()-9()4()7()11()4()4(\r)8()]TJ
/F6 1 Tf
(,)Tj
/F10 1 Tf
5.4085 0 Td
[()75()-9()4()13()18()12()-9()-4()]TJ
3.804 0 Td
[()7()-9()4()13()18()12()12()20()]TJ
/F6 1 Tf
(,)Tj
3.8948 0 Td
(and)Tj
1.7291 0 Td
(hookworm)Tj
4.6375 0 Td
(\()Tj
/F10 1 Tf
[()28(\r)7()7()22()11()11()]TJ
3.6283 0 Td
[()16( )6(\r)2()-9()4()7()16()18()-4()]TJ
/F6 1 Tf
4.7508 0 Td
(and)Tj
/F10 1 Tf
-33.029 -1.2982 Td
[()30()6()-9()3()4()7()9()11()11( )6()]TJ
5.2667 0 Td
[()12()4()4()4(\r)2()6()11()4(\r)]TJ
/F6 1 Tf
(\).)Tj
4.8018 0 Td
(These)Tj
2.5682 0 Td
(parasites)Tj
3.6907 0 Td
(are)Tj
1.4457 0 Td
(transmitted)Tj
4.8699 0 Td
(by)Tj
1.1792 0 Td
(eggs)Tj
1.9332 0 Td
(present)Tj
3.1634 0 Td
(in)Tj
1.0375 0 Td
(human)Tj
3.0784 0 Td
(faeces,)Tj
-33.0347 -1.2983 Td
(which)Tj
2.6475 0 Td
(contaminate)Tj
5.2214 0 Td
(the)Tj
1.4683 0 Td
(environment)Tj
5.4312 0 Td
(in)Tj
1.0318 0 Td
(areas)Tj
2.245 0 Td
(where)Tj
2.6475 0 Td
(sanitation)Tj
4.1839 0 Td
(is)Tj
0.8448 0 Td
(poor.)Tj
2.347 0 Td
(These)Tj
2.5625 0 Td
(diseases)Tj
3.3789 0 Td
(neg-)Tj
-34.0098 -1.3039 Td
(atively)Tj
2.8006 0 Td
(impact)Tj
2.9763 0 Td
(health)Tj
2.6816 0 Td
(and)Tj
1.7291 0 Td
(development.)Tj
5.6352 0 Td
(Current)Tj
3.4243 0 Td
(STH)Tj
2.0749 0 Td
(control)Tj
3.1238 0 Td
(is)Tj
0.8447 0 Td
(based)Tj
2.4718 0 Td
(on)Tj
1.2756 0 Td
(mass)Tj
2.1996 0 Td
(drug)Tj
-31.2375 -1.2983 Td
(administration)Tj
6.1681 0 Td
(\(MDA\))Tj
3.2145 0 Td
(programs,)Tj
4.2916 0 Td
(mainly)Tj
2.9934 0 Td
(through)Tj
3.4412 0 Td
(the)Tj
1.474 0 Td
(use)Tj
1.5307 0 Td
(of)Tj
1.0148 0 Td
(albendazole)Tj
4.9323 0 Td
(\(ABZ\))Tj
2.7609 0 Td
(and)Tj
-31.8215 -1.2982 Td
(mebendazole.)Tj
5.7202 0 Td
(However,)Tj
4.0762 0 Td
(although)Tj
3.7531 0 Td
(MDA)Tj
2.5341 0 Td
(programs)Tj
4.0649 0 Td
(have)Tj
2.0636 0 Td
(been)Tj
2.1203 0 Td
(shown)Tj
2.8516 0 Td
(to)Tj
1.0205 0 Td
(reduce)Tj
2.9197 0 Td
(the)Tj
1.4683 0 Td
(preva-)Tj
-32.5925 -1.304 Td
(lence)Tj
2.2847 0 Td
(of)Tj
1.0148 0 Td
(STH)Tj
2.0749 0 Td
(infection)Tj
3.7927 0 Td
(and)Tj
1.7292 0 Td
(to)Tj
1.0261 0 Td
(control)Tj
3.1238 0 Td
(morbidity)Tj
4.2406 0 Td
(in)Tj
1.0318 0 Td
(school-age)Tj
4.4673 0 Td
(children,)Tj
3.7814 0 Td
(rapid)Tj
2.3358 0 Td
(reinfection)Tj
-30.9031 -1.2982 Td
(is)Tj
0.8503 0 Td
(common)Tj
3.8438 0 Td
(among)Tj
2.9934 0 Td
(treated)Tj
2.999 0 Td
(children)Tj
3.5546 0 Td
(and)Tj
1.7291 0 Td
(many)Tj
2.4775 0 Td
(programs)Tj
4.0649 0 Td
(fail)Tj
1.457 0 Td
(to)Tj
1.0261 0 Td
(reach)Tj
2.3981 0 Td
(coverage)Tj
3.7247 0 Td
(targets.)Tj
-31.1185 -1.2983 Td
(Optimizing)Tj
4.8302 0 Td
(methods)Tj
3.685 0 Td
(to)Tj
1.0261 0 Td
(assess)Tj
2.5228 0 Td
(treatment)Tj
4.1329 0 Td
(coverage)Tj
3.7247 0 Td
(may)Tj
1.9276 0 Td
(allow)Tj
2.3357 0 Td
(programs)Tj
4.0705 0 Td
(to)Tj
1.0205 0 Td
(more)Tj
2.3414 0 Td
(effectively)Tj
-31.6174 -1.2983 Td
(deliver)Tj
2.9366 0 Td
(MDA)Tj
2.5342 0 Td
(to)Tj
1.0204 0 Td
(populations)Tj
4.955 0 Td
(requiring)Tj
3.9685 0 Td
(treatment.)Tj
4.3596 0 Td
(We)Tj
1.6101 0 Td
(conducted)Tj
4.4277 0 Td
(a)Tj
0.6519 0 Td
(controlled)Tj
4.32 0 Td
(trial)Tj
1.8368 0 Td
(to)Tj
1.0262 0 Td
(eval-)Tj
-33.647 -1.3039 Td
(uate)Tj
1.9048 0 Td
(the)Tj
1.4684 0 Td
(serum)Tj
2.7269 0 Td
(pharmacokinetic)Tj
6.9788 0 Td
(behaviour)Tj
4.235 0 Td
(and)Tj
1.7347 0 Td
(urinary)Tj
3.1918 0 Td
(excretion)Tj
3.9515 0 Td
(of)Tj
1.0148 0 Td
(ABZ)Tj
2.0806 0 Td
(and)Tj
1.7291 0 Td
(its)Tj
1.1509 0 Td
(metabo-)Tj
-32.1673 -1.2982 Td
(lites)Tj
1.8198 0 Td
(in)Tj
1.0318 0 Td
(human)Tj
3.0784 0 Td
(volunteers.)Tj
4.6091 0 Td
(The)Tj
1.7801 0 Td
(study)Tj
2.3925 0 Td
(focused)Tj
3.2768 0 Td
(also)Tj
1.7688 0 Td
(on)Tj
1.2756 0 Td
(to)Tj
1.0261 0 Td
(evaluate,)Tj
3.685 0 Td
(by)Tj
1.1792 0 Td
(mean)Tj
2.4492 0 Td
(of)Tj
1.0148 0 Td
(non-)Tj
-30.3872 -1.2983 Td
(invasively)Tj
4.1328 0 Td
(measures,)Tj
4.1669 0 Td
(ABZ)Tj
2.0863 0 Td
(treatment)Tj
4.1329 0 Td
(coverage)Tj
3.7247 0 Td
(and)Tj
1.7291 0 Td
(adherence.)Tj
4.5468 0 Td
(The)Tj
1.7858 0 Td
(measurement)Tj
5.6693 0 Td
(of)Tj
-31.9746 -1.3039 Td
(ABZSO)Tj
3.3108 0 Td
(concentrations)Tj
6.1795 0 Td
(both)Tj
2.0579 0 Td
(in)Tj
1.0375 0 Td
(serum)Tj
2.7212 0 Td
(and)Tj
1.7292 0 Td
(urine)Tj
2.3584 0 Td
(may)Tj
1.9275 0 Td
(be)Tj
1.1509 0 Td
(useful)Tj
2.5965 0 Td
(methods)Tj
3.685 0 Td
(to)Tj
1.0261 0 Td
(monitor)Tj
-29.7805 -1.2983 Td
(adherence)Tj
4.3256 0 Td
(to)Tj
1.0261 0 Td
(ABZ)Tj
2.0806 0 Td
(treatment)Tj
4.1386 0 Td
(and)Tj
1.7291 0 Td
(serve)Tj
2.2564 0 Td
(as)Tj
1.0148 0 Td
(a)Tj
0.6519 0 Td
(more)Tj
2.3415 0 Td
(objective)Tj
3.7813 0 Td
(measurement)Tj
5.6693 0 Td
(of)Tj
1.0148 0 Td
(program)Tj
-30.03 -1.2982 Td
(coverage.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 320.9952 cm
BT
/F2 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Introduction)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 303.9874 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(The)Tj
1.7801 0 Td
(neglected)Tj
4.0025 0 Td
(tropical)Tj
3.2825 0 Td
(diseases)Tj
3.3789 0 Td
(\(NTDs\))Tj
3.3448 0 Td
(are)Tj
1.4514 0 Td
(a)Tj
0.6519 0 Td
(group)Tj
2.6079 0 Td
(of)Tj
1.0148 0 Td
(infections)Tj
4.1555 0 Td
(which)Tj
2.6476 0 Td
(affect)Tj
2.3754 0 Td
(the)Tj
1.4683 0 Td
(poorest)Tj
-32.1616 -1.2982 Td
(regions)Tj
3.1634 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(world)Tj
2.5569 0 Td
([)Tj
0.83 0.64 0.02 0 k
(1)Tj
0 g
(].)Tj
1.5987 0 Td
(Among)Tj
3.2485 0 Td
(the)Tj
1.4683 0 Td
(NTDs,)Tj
2.8913 0 Td
(Soil-transmitted)Tj
6.7124 0 Td
(helminths)Tj
4.2406 0 Td
(\(STH,)Tj
2.6419 0 Td
(the)Tj
1.4683 0 Td
(roundworm)Tj
/F10 1 Tf
-32.4734 -1.2983 Td
[()10()-3()7()16()-9()-4()]TJ
3.016 0 Td
[()12()12( )17(\n)11()-9()4()7()11()4()4(\r)8()]TJ
/F6 1 Tf
(,)Tj
5.4141 0 Td
(the)Tj
1.4684 0 Td
(whipworm)Tj
/F10 1 Tf
4.5977 0 Td
[()75()-9()4()13()18()12()-9()-4()]TJ
3.8041 0 Td
[()7()-9()4()13()18()12()12()20()]TJ
/F6 1 Tf
3.6623 0 Td
(and)Tj
1.7348 0 Td
(the)Tj
1.4684 0 Td
(two)Tj
1.7064 0 Td
(hookworm)Tj
4.6431 0 Td
(species)Tj
/F10 1 Tf
2.9934 0 Td
[()28(\r)7()7()22()11()11()]TJ
-34.5087 -1.3039 Td
[()16( )6(\r)2()-9()4()7()16()18()-4()]TJ
/F6 1 Tf
4.7451 0 Td
(and)Tj
/F10 1 Tf
1.7291 0 Td
[()30()6()-9()3()4()7()9()11()11( )6()]TJ
5.2668 0 Td
[()12()4()4()4(\r)2()6()11()4(\r)]TJ
/F6 1 Tf
(\))Tj
4.5807 0 Td
(are)Tj
1.4457 0 Td
(among)Tj
2.9934 0 Td
(the)Tj
1.474 0 Td
(most)Tj
2.2053 0 Td
(prevalent)Tj
3.9345 0 Td
(parasites)Tj
3.6907 0 Td
(worldwide,)Tj
-32.0653 -1.2983 Td
(disproportionately)Tj
7.6421 0 Td
(affecting)Tj
3.6567 0 Td
(human)Tj
3.0784 0 Td
(populations)Tj
4.9492 0 Td
(living)Tj
2.4718 0 Td
(without)Tj
3.3279 0 Td
(adequate)Tj
3.7984 0 Td
(water)Tj
2.4321 0 Td
(and)Tj
1.7291 0 Td
(sanitation)Tj
-33.0857 -1.2982 Td
([)Tj
0.83 0.64 0.02 0 k
(2)Tj
0 g
(].)Tj
1.5987 0 Td
(It)Tj
0.8617 0 Td
(is)Tj
0.8447 0 Td
(estimated)Tj
4.0762 0 Td
(that)Tj
1.7745 0 Td
(more)Tj
2.3414 0 Td
(than)Tj
2.0296 0 Td
(1.4)Tj
1.4003 0 Td
(billion)Tj
2.8063 0 Td
(people)Tj
2.8573 0 Td
(are)Tj
1.4456 0 Td
(infected)Tj
3.4186 0 Td
(with)Tj
2.0013 0 Td
(at)Tj
0.9524 0 Td
(least)Tj
1.9786 0 Td
(one)Tj
1.7007 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(four)Tj
-34.5711 -1.3039 Td
(STH)Tj
2.0636 0 Td
(species)Tj
2.9933 0 Td
([)Tj
0.83 0.64 0.02 0 k
(3)Tj
0 g
(].)Tj
1.5931 0 Td
(STH)Tj
2.0636 0 Td
(persist)Tj
2.8119 0 Td
(for)Tj
1.3777 0 Td
(years)Tj
2.2563 0 Td
(in)Tj
1.0318 0 Td
(the)Tj
1.457 0 Td
(human)Tj
3.0728 0 Td
(gastrointestinal)Tj
6.3439 0 Td
(tract,)Tj
2.262 0 Td
(negatively)Tj
4.2293 0 Td
(impacting)Tj
-33.5563 -1.2983 Td
(nutritional)Tj
4.5354 0 Td
(status,)Tj
2.7212 0 Td
(individual)Tj
4.2916 0 Td
(productivity)Tj
5.1307 0 Td
(and)Tj
1.7348 0 Td
(physical)Tj
3.4526 0 Td
(and)Tj
1.7291 0 Td
(mental)Tj
2.9877 0 Td
(development)Tj
5.4085 0 Td
([)Tj
0.83 0.64 0.02 0 k
(1)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2642 0 Td
(4)Tj
0 g
(].)Tj
1.2586 0 Td
(The)Tj
-34.5144 -1.2983 Td
(World)Tj
2.8346 0 Td
(Health)Tj
2.9196 0 Td
(Organization)Tj
5.5219 0 Td
(\(WHO\))Tj
3.3789 0 Td
(recommendations)Tj
7.5004 0 Td
(for)Tj
1.3833 0 Td
(control)Tj
3.1238 0 Td
(of)Tj
1.0148 0 Td
(STH)Tj
2.0749 0 Td
(include)Tj
3.1861 0 Td
(preventive)Tj
-32.9383 -1.3039 Td
(chemotherapy)Tj
5.947 0 Td
(through)Tj
3.4469 0 Td
(regular)Tj
3.0557 0 Td
(mass)Tj
2.1997 0 Td
(drug)Tj
2.109 0 Td
(administration)Tj
6.1681 0 Td
(\(MDA\))Tj
3.2145 0 Td
(for)Tj
1.389 0 Td
(school)Tj
2.7892 0 Td
(age)Tj
1.5421 0 Td
(children)Tj
3.5546 0 Td
(and)Tj
-35.4158 -1.2983 Td
(other)Tj
2.347 0 Td
(at-risk)Tj
2.8006 0 Td
(groups)Tj
2.9651 0 Td
(living)Tj
2.4718 0 Td
(in)Tj
1.0374 0 Td
(endemic)Tj
3.651 0 Td
(areas)Tj
2.245 0 Td
(where)Tj
2.6476 0 Td
(prevalence)Tj
4.49 0 Td
(of)Tj
1.0148 0 Td
(STH)Tj
2.0693 0 Td
(exceeds)Tj
3.2712 0 Td
(20%.)Tj
2.1543 0 Td
(Currently,)Tj
-33.1651 -1.2982 Td
(deworming)Tj
4.8302 0 Td
(is)Tj
0.8503 0 Td
(carried)Tj
3.0388 0 Td
(out)Tj
1.5533 0 Td
(with)Tj
1.9956 0 Td
(single)Tj
2.5342 0 Td
(oral)Tj
1.7745 0 Td
(dose)Tj
2.0409 0 Td
(of)Tj
1.0148 0 Td
(a)Tj
0.6576 0 Td
(benzimidazole)Tj
6.0151 0 Td
(\(BZD\))Tj
2.8176 0 Td
(anthelmintic)Tj
5.3234 0 Td
(drug)Tj
-34.4463 -1.2983 Td
(\(albendazole)Tj
5.2667 0 Td
(\(ABZ\))Tj
2.7666 0 Td
(or)Tj
1.0998 0 Td
(mebendazole)Tj
5.4935 0 Td
(\(MBZ\)\))Tj
3.3109 0 Td
(once)Tj
2.1259 0 Td
(or)Tj
1.0942 0 Td
(twice)Tj
2.3187 0 Td
(year)Tj
1.9049 0 Td
(depending)Tj
4.4674 0 Td
(on)Tj
1.2756 0 Td
(baseline)Tj
3.4299 0 Td
(preva-)Tj
-34.5541 -1.3039 Td
(lence)Tj
2.2847 0 Td
([)Tj
0.83 0.64 0.02 0 k
(5)Tj
0 g
(].)Tj
-1.0885 -1.2983 Td
(Despite)Tj
3.2484 0 Td
(significant)Tj
4.3881 0 Td
(success)Tj
3.101 0 Td
(in)Tj
1.0375 0 Td
(scaling)Tj
2.965 0 Td
(up)Tj
1.2643 0 Td
(deworming)Tj
4.8358 0 Td
(programs)Tj
4.0649 0 Td
(and)Tj
1.7291 0 Td
(reducing)Tj
3.7758 0 Td
(associated)Tj
-31.6061 -1.2982 Td
(morbidity,)Tj
4.4617 0 Td
(program)Tj
3.7076 0 Td
(coverage)Tj
3.7247 0 Td
(globally)Tj
3.3222 0 Td
(is)Tj
0.8504 0 Td
(still)Tj
1.6384 0 Td
(less)Tj
1.6101 0 Td
(than)Tj
2.0296 0 Td
(optimal)Tj
3.3108 0 Td
([)Tj
0.83 0.64 0.02 0 k
(6)Tj
0 g
(].)Tj
1.5988 0 Td
(In)Tj
1.1111 0 Td
(addition,)Tj
3.8211 0 Td
(some)Tj
2.3301 0 Td
(areas)Tj
-33.5166 -1.3039 Td
(report)Tj
2.7099 0 Td
(apparent)Tj
3.7643 0 Td
(reductions)Tj
4.4731 0 Td
(in)Tj
1.0375 0 Td
(treatment)Tj
4.1328 0 Td
(efficacy)Tj
3.2259 0 Td
(following)Tj
3.9741 0 Td
(multiple)Tj
3.5716 0 Td
(rounds)Tj
3.0614 0 Td
(of)Tj
1.0148 0 Td
(MDA.)Tj
2.7553 0 Td
(Treat-)Tj
-33.7207 -1.2983 Td
(ment)Tj
2.3073 0 Td
(failure)Tj
2.778 0 Td
(may)Tj
1.9275 0 Td
(be)Tj
1.1509 0 Td
(related)Tj
2.948 0 Td
(to)Tj
1.0261 0 Td
(poor)Tj
2.1203 0 Td
(programmatic)Tj
5.9471 0 Td
(coverage)Tj
3.7247 0 Td
(or)Tj
1.0998 0 Td
(adherence,)Tj
4.5468 0 Td
(reduced)Tj
3.4469 0 Td
(drug)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 183.2882 23.6976 re
W* n
q
183.2315 0 0 23.6409 36 741.3165 cm
q
/I0 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 449.1212 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Urinary)Tj
3.3874 0 Td
(excretion)Tj
4.2024 0 Td
(of)Tj
1.0417 0 Td
(ABZ/meta)Tj
4.3937 0 Td
(bolites)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
163.5591 34.9228 m
317.7071 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(Neglected)Tj
4.6417 0 Td
(Tropical)Tj
3.7135 0 Td
(Disease)Tj
3.5433 0 Td
(s)Tj
0.7158 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8197 0 Td
(1/journal.pn)Tj
5.1237 0 Td
(td.00059)Tj
3.8197 0 Td
(45)Tj
0 g
2.0905 0 Td
(January)Tj
3.7205 0 Td
(18,)Tj
1.5804 0 Td
(2018)Tj
23.6269 0 Td
(2)Tj
0.7654 0 Td
(/)Tj
0.496 0 Td
(15)Tj
/F8 1 Tf
-0.025 Tc
-66.402 84.0904 Td
(design,)Tj
2.8984 0 Td
(data)Tj
1.7929 0 Td
(collection)Tj
3.7418 0 Td
(and)Tj
1.5874 0 Td
(analysis,)Tj
3.4087 0 Td
(decision)Tj
3.2953 0 Td
(to)Tj
-16.7245 -1.3748 Td
(publish,)Tj
3.1464 0 Td
(or)Tj
0.9993 0 Td
(preparation)Tj
4.4433 0 Td
(of)Tj
0.9496 0 Td
(the)Tj
1.3677 0 Td
(manuscript.)Tj
/F7 1 Tf
-10.9063 -2.126 Td
(Competing)Tj
4.3795 0 Td
(interests)Tj
3.3307 0 Td
(:)Tj
/F8 1 Tf
0.4819 0 Td
(The)Tj
1.5875 0 Td
(authors)Tj
3.0401 0 Td
(have)Tj
1.963 0 Td
(declared)Tj
-14.7827 -1.3749 Td
(that)Tj
1.6228 0 Td
(no)Tj
1.1693 0 Td
(competing)Tj
4.1599 0 Td
(interests)Tj
ET
endstream
endobj
27 0 obj
<>stream
endstream
endobj
28 0 obj
<>stream
endstream
endobj
29 0 obj
<>stream
endstream
endobj
30 0 obj
<>stream
endstream
endobj
31 0 obj
<>stream
endstream
endobj
32 0 obj
<>stream
endstream
endobj
33 0 obj
<>stream
BT
10.3394 79.2147 Td
(exist.)Tj
ET
Q
endstream
endobj
34 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 12 0 R/Annots 36 0 R/Contents 37 0 R/TrimBox[0 0 612 792]>>
endobj
36 0 obj
[38 0 R 39 0 R 40 0 R 41 0 R 42 0 R 43 0 R 44 0 R 45 0 R 46 0 R 47 0 R 48 0 R 49 0 R 50 0 R 51 0 R 52 0 R 53 0 R 54 0 R]
endobj
38 0 obj
<>/Border[0 0 0]/Dest(Rpntd.0005945.ref007)>>
endobj
39 0 obj
<>/Border[0 0 0]/Dest(Rpntd.0005945.ref006)>>
endobj
40 0 obj
<>/Border[0 0 0]/Dest(Rpntd.0005945.ref008)>>
endobj
41 0 obj
<>/Border[0 0 0]/Dest(Rpntd.0005945.ref009)>>
endobj
42 0 obj
<>/Border[0 0 0]/Dest(Rpntd.0005945.ref010)>>
endobj
43 0 obj
<>/Border[0 0 0]/Dest(Rpntd.0005945.ref011)>>
endobj
44 0 obj
<>/Border[0 0 0]/Dest(Rpntd.0005945.ref012)>>
endobj
45 0 obj
<>/Border[0 0 0]/Dest(Rpntd.0005945.ref013)>>
endobj
46 0 obj
<>/Border[0 0 0]/Dest(Rpntd.0005945.ref018)>>
endobj
47 0 obj
<>/Border[0 0 0]/Dest(Rpntd.0005945.ref015)>>
endobj
48 0 obj
<>/Border[0 0 0]/Dest(Rpntd.0005945.ref016)>>
endobj
49 0 obj
<>/Border[0 0 0]/Dest(Rpntd.0005945.ref013)>>
endobj
50 0 obj
<>/Border[0 0 0]/Dest(Rpntd.0005945.ref019)>>
endobj
51 0 obj
<>/Border[0 0 0]/Dest(Rpntd.0005945.ref021)>>
endobj
52 0 obj
<>/Border[0 0 0]/Dest(Rpntd.0005945.ref022)>>
endobj
53 0 obj
<>/Border[0 0 0]/A 55 0 R>>
endobj
55 0 obj
<>
endobj
54 0 obj
<>/Border[0 0 0]/A 56 0 R>>
endobj
56 0 obj
<>
endobj
37 0 obj
[57 0 R 58 0 R 59 0 R 60 0 R 61 0 R 62 0 R 63 0 R 64 0 R 65 0 R 66 0 R 67 0 R 68 0 R 69 0 R 70 0 R 71 0 R 72 0 R 73 0 R]
endobj
57 0 obj
<>stream
q
0.83 0.64 0.02 0 k
399.9685 641.3102 m
404.7307 641.3102 l
h
f*
463.6346 511.3134 m
468.3969 511.3134 l
h
f*
223.9937 472.3087 m
228.7559 472.3087 l
h
f*
554.9102 433.3039 m
559.6724 433.3039 l
h
f*
484.4976 394.2992 m
494.022 394.2992 l
h
f*
461.1402 381.3165 m
470.6646 381.3165 l
h
f*
223.8803 368.3339 m
233.348 368.3339 l
h
f*
265.0961 342.3118 m
274.6205 342.3118 l
h
f*
279.7795 342.3118 m
289.3039 342.3118 l
h
f*
480.0189 303.3071 m
489.5433 303.3071 l
h
f*
494.022 303.3071 m
503.5465 303.3071 l
h
f*
452.9764 290.3244 m
462.5008 290.3244 l
h
f*
466.9228 290.3244 m
476.4472 290.3244 l
h
f*
481.6063 290.3244 m
491.1307 290.3244 l
h
f*
551.3953 290.3244 m
560.863 290.3244 l
h
f*
277.9087 81.9213 m
342.822 81.9213 l
h
f*
0 g
1 j
1 J
0 w
10 0 0 10 200.0125 707.4141 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(efficacy)Tj
3.2201 0 Td
(through)Tj
3.4469 0 Td
(suboptimal)Tj
4.7055 0 Td
(drug)Tj
2.1089 0 Td
(formulation,)Tj
5.2611 0 Td
(poor)Tj
2.1203 0 Td
(drug)Tj
2.1146 0 Td
(absorption)Tj
4.5411 0 Td
(or)Tj
1.0942 0 Td
(the)Tj
1.4683 0 Td
(development)Tj
5.4142 0 Td
(of)Tj
-35.4952 -1.3039 Td
(resistance.)Tj
4.3539 0 Td
(It)Tj
0.8618 0 Td
(is)Tj
0.8447 0 Td
(critical)Tj
2.9537 0 Td
(to)Tj
1.0261 0 Td
(differentiate)Tj
5.0797 0 Td
(a)Tj
0.6519 0 Td
(lack)Tj
1.8199 0 Td
(of)Tj
1.0147 0 Td
(coverage)Tj
3.7247 0 Td
(or)Tj
1.0942 0 Td
(adherence)Tj
4.3257 0 Td
(to)Tj
1.0261 0 Td
(drug)Tj
2.109 0 Td
(from)Tj
2.2053 0 Td
(issues)Tj
-33.0914 -1.2982 Td
(related)Tj
2.9423 0 Td
(to)Tj
1.0261 0 Td
(drug)Tj
2.1147 0 Td
(quality)Tj
2.9536 0 Td
(or)Tj
1.0999 0 Td
(the)Tj
1.4683 0 Td
(development)Tj
5.4085 0 Td
(of)Tj
1.0148 0 Td
(drug)Tj
2.1146 0 Td
(resistance.)Tj
4.354 0 Td
(Current)Tj
3.4242 0 Td
(coverage)Tj
3.7247 0 Td
(estimates)Tj
3.9062 0 Td
(rely)Tj
-35.5519 -1.2983 Td
(on)Tj
1.2755 0 Td
(subjective)Tj
4.1613 0 Td
(reporting)Tj
3.9911 0 Td
(of)Tj
1.0148 0 Td
(coverage)Tj
3.7191 0 Td
(and)Tj
1.7347 0 Td
(adherence)Tj
4.32 0 Td
(through)Tj
3.4469 0 Td
(an)Tj
1.2019 0 Td
(interview)Tj
3.9571 0 Td
(based)Tj
2.4718 0 Td
(coverage)Tj
3.7247 0 Td
(sur-)Tj
-35.0189 -1.2983 Td
(vey.)Tj
1.7744 0 Td
(Such)Tj
2.177 0 Td
(instruments)Tj
5.0457 0 Td
(are)Tj
1.4513 0 Td
(prone)Tj
2.5852 0 Td
(to)Tj
1.0261 0 Td
(reporter)Tj
3.5036 0 Td
(and)Tj
1.7291 0 Td
(interviewer)Tj
4.7509 0 Td
(bias)Tj
1.7914 0 Td
(and)Tj
1.7292 0 Td
(may)Tj
1.9275 0 Td
(not)Tj
1.5761 0 Td
(adequately)Tj
-31.0675 -1.3039 Td
(reflect)Tj
2.6928 0 Td
(true)Tj
1.8426 0 Td
(treatment)Tj
4.1328 0 Td
(coverage)Tj
3.7247 0 Td
(and/or)Tj
2.9367 0 Td
(adherence)Tj
4.3257 0 Td
([)Tj
0.83 0.64 0.02 0 k
(7)Tj
0 g
(].)Tj
-18.4591 -1.2982 Td
(The)Tj
1.7858 0 Td
(development)Tj
5.4084 0 Td
(of)Tj
1.0148 0 Td
(improved)Tj
4.1103 0 Td
(tools)Tj
2.1373 0 Td
(to)Tj
1.0261 0 Td
(accurately)Tj
4.2576 0 Td
(determine)Tj
4.32 0 Td
(treatment)Tj
4.1385 0 Td
(coverage)Tj
3.7247 0 Td
(and)Tj
1.7292 0 Td
(adher-)Tj
-34.8489 -1.2983 Td
(ence)Tj
2.0352 0 Td
(may)Tj
1.9332 0 Td
(be)Tj
1.1509 0 Td
(important)Tj
4.2803 0 Td
(to)Tj
1.0261 0 Td
(enable)Tj
2.8006 0 Td
(programs)Tj
4.0649 0 Td
(to)Tj
1.0261 0 Td
(more)Tj
2.3414 0 Td
(accurately)Tj
4.2576 0 Td
(report)Tj
2.7099 0 Td
(true)Tj
1.8425 0 Td
(coverage)Tj
3.7191 0 Td
(of)Tj
1.0148 0 Td
(MDA)Tj
-34.2026 -1.3039 Td
(and)Tj
1.7291 0 Td
(to)Tj
1.0261 0 Td
(respond)Tj
3.4753 0 Td
(to)Tj
1.0261 0 Td
(situations)Tj
4.0875 0 Td
(where)Tj
2.6532 0 Td
(treatment)Tj
4.1329 0 Td
(failure)Tj
2.778 0 Td
(is)Tj
0.8504 0 Td
(suspected.)Tj
4.3086 0 Td
(In)Tj
1.1055 0 Td
(fact,)Tj
1.8935 0 Td
(validation)Tj
4.2009 0 Td
(of)Tj
1.0148 0 Td
(compli-)Tj
-34.2819 -1.2983 Td
(ance)Tj
2.0466 0 Td
(is)Tj
0.8503 0 Td
(extremely)Tj
4.1443 0 Td
(important)Tj
4.2803 0 Td
(also)Tj
1.7688 0 Td
(for)Tj
1.3889 0 Td
(lymphatic)Tj
4.2066 0 Td
(filariasis)Tj
3.515 0 Td
(elimination,)Tj
5.0739 0 Td
(and)Tj
1.7292 0 Td
(like)Tj
1.6554 0 Td
(with)Tj
1.9956 0 Td
(STH,)Tj
2.3017 0 Td
(there)Tj
-34.9566 -1.2983 Td
(are)Tj
1.4456 0 Td
(currently)Tj
3.8891 0 Td
(no)Tj
1.2756 0 Td
(tools)Tj
2.1373 0 Td
(to)Tj
1.0261 0 Td
(use)Tj
1.5307 0 Td
(to)Tj
1.0262 0 Td
(measure)Tj
3.583 0 Td
(it.)Tj
-14.7174 -1.3039 Td
(Accurate)Tj
3.8097 0 Td
(measurement)Tj
5.6693 0 Td
(and)Tj
1.7291 0 Td
(determination)Tj
5.9584 0 Td
(of)Tj
1.0148 0 Td
(coverage)Tj
3.719 0 Td
(and)Tj
1.7291 0 Td
(adherence)Tj
4.3257 0 Td
(to)Tj
1.0261 0 Td
(MDA)Tj
2.5342 0 Td
(has)Tj
1.542 0 Td
(become)Tj
-34.2536 -1.2982 Td
(even)Tj
2.0692 0 Td
(more)Tj
2.3414 0 Td
(critical)Tj
2.9537 0 Td
(as)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(STH)Tj
2.075 0 Td
(community)Tj
4.8869 0 Td
(begins)Tj
2.7893 0 Td
(to)Tj
1.0261 0 Td
(think)Tj
2.3584 0 Td
(beyond)Tj
3.1861 0 Td
(control)Tj
3.1238 0 Td
(towards)Tj
3.4015 0 Td
(the)Tj
1.4684 0 Td
(possibil-)Tj
-34.1629 -1.2983 Td
(ity)Tj
1.2415 0 Td
(of)Tj
1.0148 0 Td
(disease)Tj
3.0161 0 Td
(elimination.)Tj
5.0739 0 Td
(Although)Tj
4.0025 0 Td
(annual)Tj
2.9594 0 Td
(MDA)Tj
2.5341 0 Td
(may)Tj
1.9276 0 Td
(reduce)Tj
2.914 0 Td
(the)Tj
1.474 0 Td
(prevalence)Tj
4.4844 0 Td
(of)Tj
1.0148 0 Td
(STH)Tj
2.0749 0 Td
(infection)Tj
-33.732 -1.3039 Td
(and)Tj
1.7291 0 Td
(control)Tj
3.1237 0 Td
(morbidity)Tj
4.2406 0 Td
(in)Tj
1.0318 0 Td
(school-age)Tj
4.4674 0 Td
(children,)Tj
3.7814 0 Td
(reinfection)Tj
4.5864 0 Td
(following)Tj
3.9799 0 Td
(treatment)Tj
4.1328 0 Td
(is)Tj
0.8504 0 Td
(common)Tj
3.8438 0 Td
(and)Tj
-35.7673 -1.2983 Td
(this)Tj
1.6724 0 Td
(strategy)Tj
3.3278 0 Td
(is)Tj
0.8448 0 Td
(likely)Tj
2.3584 0 Td
(to)Tj
1.0261 0 Td
(be)Tj
1.1452 0 Td
(insufficient)Tj
4.7281 0 Td
(to)Tj
1.0262 0 Td
(break)Tj
2.4548 0 Td
(STH)Tj
2.0749 0 Td
(transmission)Tj
5.3631 0 Td
([)Tj
0.83 0.64 0.02 0 k
(6)Tj
0 g
(].)Tj
1.5988 0 Td
(Recent)Tj
2.9593 0 Td
(mathematical)Tj
-30.5799 -1.2982 Td
(modelling)Tj
4.2689 0 Td
(studies)Tj
2.9877 0 Td
(suggests)Tj
3.4809 0 Td
(that)Tj
1.7802 0 Td
(MDA)Tj
2.5341 0 Td
(might)Tj
2.5965 0 Td
(be)Tj
1.1509 0 Td
(sufficient)Tj
3.9118 0 Td
(to)Tj
1.0261 0 Td
(interrupt)Tj
3.8438 0 Td
(STH)Tj
2.0749 0 Td
(transmission)Tj
5.3631 0 Td
(if)Tj
0.7767 0 Td
(new)Tj
-35.7956 -1.2983 Td
(strategies,)Tj
4.1498 0 Td
(including)Tj
4.0366 0 Td
(expanding)Tj
4.422 0 Td
(MDA)Tj
2.5285 0 Td
(to)Tj
1.0261 0 Td
(adults)Tj
2.6192 0 Td
(and/or)Tj
2.9367 0 Td
(treating)Tj
3.3278 0 Td
(children)Tj
3.5546 0 Td
(more)Tj
2.3414 0 Td
(frequently,)Tj
4.5355 0 Td
(are)Tj
-35.4782 -1.3039 Td
(used)Tj
2.0579 0 Td
([)Tj
0.83 0.64 0.02 0 k
(8)Tj
0 g
(].)Tj
1.6044 0 Td
(These)Tj
2.5625 0 Td
(models)Tj
3.1067 0 Td
(suggest)Tj
3.1238 0 Td
(that)Tj
1.7745 0 Td
(exceptionally)Tj
5.4765 0 Td
(high)Tj
2.0069 0 Td
(coverage)Tj
3.7247 0 Td
(and)Tj
1.7291 0 Td
(adherence)Tj
4.3257 0 Td
(will)Tj
1.6611 0 Td
(be)Tj
1.1508 0 Td
(needed)Tj
-34.3046 -1.2983 Td
(to)Tj
1.0261 0 Td
(interrupt)Tj
3.8437 0 Td
(transmission)Tj
5.3632 0 Td
(through)Tj
3.4469 0 Td
(MDA)Tj
2.5285 0 Td
(alone.)Tj
-15.0122 -1.2983 Td
(The)Tj
1.7858 0 Td
(widespread)Tj
4.7565 0 Td
(use)Tj
1.5307 0 Td
(of)Tj
1.0148 0 Td
(BZD)Tj
2.1373 0 Td
(anthelmintics,)Tj
5.9074 0 Td
(particularly)Tj
4.8132 0 Td
(the)Tj
1.4683 0 Td
(methylcarbamate)Tj
7.1376 0 Td
(derivatives)Tj
-31.7478 -1.3039 Td
(such)Tj
2.0579 0 Td
(as)Tj
1.0148 0 Td
(ABZ,)Tj
2.313 0 Td
(is)Tj
0.8448 0 Td
(based)Tj
2.4718 0 Td
(on)Tj
1.2755 0 Td
(their)Tj
2.109 0 Td
(high)Tj
2.0069 0 Td
(efficacy,)Tj
3.4469 0 Td
(low)Tj
1.6611 0 Td
(toxicity,)Tj
3.4242 0 Td
(and)Tj
1.7292 0 Td
(broad-spectrum)Tj
6.6613 0 Td
(of)Tj
1.0148 0 Td
(activity)Tj
3.1181 0 Td
([)Tj
0.83 0.64 0.02 0 k
(9)Tj
0 g
(].)Tj
-35.1493 -1.2982 Td
(While)Tj
2.6475 0 Td
(there)Tj
2.2677 0 Td
(are)Tj
1.4457 0 Td
(limited)Tj
3.0727 0 Td
(data)Tj
1.9105 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
1.474 0 Td
(pharmacokinetics)Tj
7.336 0 Td
(\(PK\))Tj
2.1317 0 Td
(and)Tj
1.7348 0 Td
(urinary)Tj
3.1918 0 Td
(excretion)Tj
3.9514 0 Td
(of)Tj
1.0148 0 Td
(ABZ)Tj
2.0806 0 Td
(and)Tj
-35.5348 -1.2983 Td
(its)Tj
1.1451 0 Td
(metabolites)Tj
4.8019 0 Td
(in)Tj
1.0318 0 Td
(humans,)Tj
3.6623 0 Td
(it)Tj
0.7824 0 Td
(is)Tj
0.8447 0 Td
(known)Tj
3.0047 0 Td
(is)Tj
0.8447 0 Td
(that)Tj
1.7802 0 Td
(after)Tj
2.0296 0 Td
(absorption,)Tj
4.7622 0 Td
(BZD)Tj
2.1373 0 Td
(compounds)Tj
4.9549 0 Td
(are)Tj
1.4457 0 Td
(extensively)Tj
-33.2275 -1.3039 Td
(metabolized.)Tj
5.312 0 Td
(Biotransformation)Tj
7.6252 0 Td
(takes)Tj
2.2337 0 Td
(place)Tj
2.2677 0 Td
(predominantly)Tj
6.1795 0 Td
(in)Tj
1.0374 0 Td
(the)Tj
1.4684 0 Td
(liver)Tj
1.9842 0 Td
([)Tj
0.83 0.64 0.02 0 k
(10)Tj
0 g
(],)Tj
2.075 0 Td
(although)Tj
3.7587 0 Td
(meta-)Tj
-33.9418 -1.2983 Td
(bolic)Tj
2.1713 0 Td
(activity)Tj
3.1181 0 Td
(is)Tj
0.8447 0 Td
(apparent)Tj
3.7644 0 Td
(in)Tj
1.0374 0 Td
(extrahepatic)Tj
5.1024 0 Td
(tissues)Tj
2.8176 0 Td
(such)Tj
2.0636 0 Td
(as)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(lungs)Tj
2.3698 0 Td
([)Tj
0.83 0.64 0.02 0 k
(11)Tj
0 g
(])Tj
1.8482 0 Td
(and)Tj
1.7348 0 Td
(gastrointestinal)Tj
6.3495 0 Td
(\(GI\))Tj
-35.7049 -1.2983 Td
(tract)Tj
2.0466 0 Td
([)Tj
0.83 0.64 0.02 0 k
(12)Tj
0 g
(])Tj
-0.8504 -1.2982 Td
(Consequently,)Tj
5.9584 0 Td
(ABZ)Tj
2.0862 0 Td
(\(the)Tj
1.8085 0 Td
(parent)Tj
2.812 0 Td
(compound\))Tj
4.9379 0 Td
(is)Tj
0.8504 0 Td
(undetectable)Tj
5.3007 0 Td
(in)Tj
1.0318 0 Td
(the)Tj
1.4741 0 Td
(systemic)Tj
3.6283 0 Td
(circulation)Tj
4.5354 0 Td
(after)Tj
-35.6199 -1.3039 Td
(administration)Tj
6.1681 0 Td
([)Tj
0.83 0.64 0.02 0 k
(13)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(18)Tj
0 g
(].)Tj
3.5433 0 Td
(ABZ)Tj
2.0863 0 Td
(is)Tj
0.8504 0 Td
(rapidly)Tj
3.0387 0 Td
(oxidized)Tj
3.617 0 Td
(into)Tj
1.8425 0 Td
(its)Tj
1.1452 0 Td
(active)Tj
2.5228 0 Td
(metabolite)Tj
4.439 0 Td
(ABZ-sulphoxide)Tj
-29.2533 -1.2983 Td
(\(ABZSO\))Tj
3.9854 0 Td
(and)Tj
1.7292 0 Td
(further)Tj
3.0273 0 Td
(liver)Tj
1.9843 0 Td
(oxidative)Tj
3.8664 0 Td
(and)Tj
1.7291 0 Td
(hydrolytic)Tj
4.2973 0 Td
(metabolism)Tj
4.9039 0 Td
(produces)Tj
3.8778 0 Td
(ABZ)Tj
2.0863 0 Td
(sulphone)Tj
-31.487 -1.2983 Td
(\(ABZSO)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 234.2551 315.7228 cm
BT
/F6 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(2)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 237.8267 317.4236 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(\))Tj
0.5612 0 Td
(and)Tj
1.7291 0 Td
(albendazole)Tj
4.9323 0 Td
(amino)Tj
2.7949 0 Td
(sulphone)Tj
3.8778 0 Td
(\(ABZ-SO2NH)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 439.5401 315.7228 cm
BT
/F6 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(2)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 443.1118 317.4236 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(\),)Tj
0.7823 0 Td
(respectively.)Tj
5.1137 0 Td
(ABZSO)Tj
3.3052 0 Td
(and)Tj
-33.5109 -1.3039 Td
(ABZSO)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 230.8535 302.7401 cm
BT
/F6 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(2)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 236.6362 304.3842 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(are)Tj
1.4456 0 Td
(the)Tj
1.474 0 Td
(metabolites)Tj
4.8019 0 Td
(mainly)Tj
2.9933 0 Td
(found)Tj
2.6192 0 Td
(in)Tj
1.0318 0 Td
(the)Tj
1.4741 0 Td
(systemic)Tj
3.6283 0 Td
(circulation)Tj
4.5297 0 Td
([)Tj
0.83 0.64 0.02 0 k
(15)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7405 0 Td
(16)Tj
0 g
(].)Tj
1.7348 0 Td
(ABZSO)Tj
3.3051 0 Td
(appears)Tj
-34.4406 -1.2982 Td
(to)Tj
1.0261 0 Td
(be)Tj
1.1509 0 Td
(the)Tj
1.4683 0 Td
(main)Tj
2.2903 0 Td
(metabolite)Tj
4.4447 0 Td
(that)Tj
1.7745 0 Td
(is)Tj
0.8504 0 Td
(recoverable)Tj
4.8018 0 Td
(in)Tj
1.0375 0 Td
(human)Tj
3.0784 0 Td
(plasma)Tj
3.0331 0 Td
([)Tj
0.83 0.64 0.02 0 k
(13)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7348 0 Td
(19)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(21)Tj
0 g
(])Tj
2.982 0 Td
(and)Tj
1.7291 0 Td
(in)Tj
1.0375 0 Td
(urine)Tj
2.3584 0 Td
([)Tj
0.83 0.64 0.02 0 k
(22)Tj
0 g
(].)Tj
-0.017 Tc
-33.6016 -1.2983 Td
(As)Tj
1.2416 0 Td
(part)Tj
1.7914 0 Td
(of)Tj
0.9864 0 Td
(the)Tj
1.4287 0 Td
(DeWorm3)Tj
4.4277 0 Td
(project,)Tj
3.1407 0 Td
(a)Tj
0.6407 0 Td
(large)Tj
2.0976 0 Td
(series)Tj
2.3471 0 Td
(of)Tj
0.9921 0 Td
(community)Tj
4.7678 0 Td
(cluster)Tj
2.778 0 Td
(randomized)Tj
4.9322 0 Td
(trials)Tj
2.1203 0 Td
(to)Tj
-34.8885 -1.3039 Td
(determine)Tj
4.2065 0 Td
(the)Tj
1.4287 0 Td
(feasibility)Tj
3.8891 0 Td
(of)Tj
0.9921 0 Td
(interrupting)Tj
4.9662 0 Td
(STH)Tj
2.0353 0 Td
(transmission,)Tj
5.4255 0 Td
(we)Tj
1.2982 0 Td
(sought)Tj
2.829 0 Td
(1\))Tj
1.0091 0 Td
(to)Tj
1.0035 0 Td
(develop)Tj
3.2258 0 Td
(and)Tj
1.6894 0 Td
(validate)Tj
-33.9984 -1.2983 Td
(an)Tj
1.1735 0 Td
(analytical)Tj
3.8777 0 Td
(method)Tj
3.2485 0 Td
(to)Tj
0.9978 0 Td
(quantify)Tj
3.4412 0 Td
(concentrations)Tj
5.9981 0 Td
(of)Tj
0.9865 0 Td
(ABZ)Tj
2.0466 0 Td
(and)Tj
1.6951 0 Td
(its)Tj
1.1055 0 Td
(metabolites,)Tj
4.8755 0 Td
(ABZSO)Tj
3.2428 0 Td
(and)Tj
-32.6888 -1.2982 Td
(ABZSO)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 230.2299 237.7133 cm
BT
/F6 1 Tf
1 TL
-0.0226 Tc
0 0 Td
(2)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 233.6314 239.4141 cm
BT
/F6 1 Tf
1 TL
-0.017 Tc
0 0 Td
(,)Tj
0.4308 0 Td
(in)Tj
1.0035 0 Td
(human)Tj
3.0103 0 Td
(serum)Tj
2.6533 0 Td
(and)Tj
1.6894 0 Td
(urine)Tj
2.2904 0 Td
(samples,)Tj
3.4979 0 Td
(2\))Tj
1.0091 0 Td
(to)Tj
0.9922 0 Td
(conduct)Tj
3.3845 0 Td
(a)Tj
0.635 0 Td
(study)Tj
2.3187 0 Td
(of)Tj
0.9864 0 Td
(the)Tj
1.4287 0 Td
(serum)Tj
2.6532 0 Td
(pharmacokinet-)Tj
-31.3452 -1.3039 Td
(ics)Tj
1.2302 0 Td
(and)Tj
1.6951 0 Td
(urinary)Tj
3.101 0 Td
(excretion)Tj
3.8324 0 Td
(of)Tj
0.9865 0 Td
(ABZ)Tj
2.0466 0 Td
(and)Tj
1.6894 0 Td
(its)Tj
1.1112 0 Td
(metabolites)Tj
4.6601 0 Td
(in)Tj
1.0091 0 Td
(human)Tj
3.0161 0 Td
(volunteers,)Tj
4.4617 0 Td
(and)Tj
1.6951 0 Td
(3\))Tj
1.0091 0 Td
(to)Tj
0.9978 0 Td
(determine)Tj
-32.5414 -1.2982 Td
(the)Tj
1.4286 0 Td
(optimal)Tj
3.2201 0 Td
(and)Tj
1.6894 0 Td
(the)Tj
1.4343 0 Td
(longest)Tj
2.9764 0 Td
(time)Tj
1.9786 0 Td
(period)Tj
2.7552 0 Td
(after)Tj
1.9673 0 Td
(treatment)Tj
4.0195 0 Td
(when)Tj
2.3527 0 Td
(either)Tj
2.4548 0 Td
(ABZ)Tj
2.0466 0 Td
(and/or)Tj
2.8573 0 Td
(its)Tj
1.1112 0 Td
(metabolites)Tj
-32.292 -1.2983 Td
(can)Tj
1.5874 0 Td
(be)Tj
1.1225 0 Td
(measured)Tj
4.0024 0 Td
(in)Tj
1.0148 0 Td
(urine)Tj
2.2904 0 Td
(as)Tj
0.9864 0 Td
(an)Tj
1.1792 0 Td
(indirect)Tj
3.2428 0 Td
(assessment)Tj
4.4844 0 Td
(of)Tj
0.9865 0 Td
(an)Tj
1.1792 0 Td
(individual's)Tj
4.7054 0 Td
(adherence)Tj
4.2066 0 Td
(to)Tj
0.9978 0 Td
(treatment.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 170.022 cm
BT
/F2 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Materials)Tj
4.5071 0 Td
(and)Tj
1.989 0 Td
(methods)Tj
/F11 1 Tf
-6.4961 -1.5023 Td
(Ethical)Tj
3.1417 0 Td
(aspects)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 134.9858 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(The)Tj
1.7801 0 Td
(experimental)Tj
5.4595 0 Td
(protocol)Tj
3.6 0 Td
(and)Tj
1.7291 0 Td
(Informed)Tj
4.0422 0 Td
(Consent)Tj
3.5716 0 Td
(Form)Tj
2.4491 0 Td
(\(ICF\))Tj
2.4265 0 Td
(were)Tj
2.1259 0 Td
(approved)Tj
3.9742 0 Td
(by)Tj
1.1792 0 Td
(the)Tj
1.4683 0 Td
(Bioethics)Tj
-33.8057 -1.2982 Td
(Committee)Tj
4.7394 0 Td
(at)Tj
0.9525 0 Td
(the)Tj
1.4683 0 Td
(Colegio)Tj
3.2995 0 Td
(Me)Tj
0 Tc
0.9128 0.051 Td
()Tj
-0.004 Tc
0.4025 -0.051 Td
(dico)Tj
1.9445 0 Td
(de)Tj
1.1736 0 Td
(Salta)Tj
2.1089 0 Td
(\(Argentina\).)Tj
-15.8058 -1.2983 Td
(All)Tj
1.4003 0 Td
(the)Tj
1.4683 0 Td
(volunteers)Tj
4.3823 0 Td
(provided)Tj
3.8154 0 Td
(written)Tj
3.1125 0 Td
(consent)Tj
3.3278 0 Td
(for)Tj
1.389 0 Td
(their)Tj
2.109 0 Td
(participation)Tj
5.3687 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4684 0 Td
(study)Tj
2.3924 0 Td
(before)Tj
2.7382 0 Td
(any)Tj
-35.206 -1.3039 Td
(study)Tj
2.3867 0 Td
(procedures)Tj
4.6771 0 Td
(commenced.)Tj
5.3575 0 Td
(Volunteers)Tj
4.6261 0 Td
(received)Tj
3.5319 0 Td
(a)Tj
0.6577 0 Td
(small)Tj
2.3244 0 Td
(stipend)Tj
3.1634 0 Td
(for)Tj
1.389 0 Td
(their)Tj
2.1033 0 Td
(collaboration.)Tj
5.7429 0 Td
(The)Tj
-35.96 -1.2983 Td
(trial)Tj
1.8368 0 Td
(is)Tj
0.8447 0 Td
(registered)Tj
4.1556 0 Td
(at)Tj
0.83 0.64 0.02 0 k
0.9524 0 Td
(clinicaltrials.gov)Tj
0 g
6.7067 0 Td
(\(REF)Tj
2.2791 0 Td
(NCT03192449\).)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 183.2882 23.6976 re
W* n
q
183.2315 0 0 23.6409 36 741.3165 cm
q
/I0 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 449.1212 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Urinary)Tj
3.3874 0 Td
(excretion)Tj
4.2024 0 Td
(of)Tj
1.0417 0 Td
(ABZ/meta)Tj
4.3937 0 Td
(bolites)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
163.5591 34.9228 m
317.7071 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(Neglected)Tj
4.6417 0 Td
(Tropical)Tj
3.7135 0 Td
(Disease)Tj
3.5433 0 Td
(s)Tj
0.7158 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8197 0 Td
(1/journal.pn)Tj
5.1237 0 Td
(td.00059)Tj
3.8197 0 Td
(45)Tj
0 g
2.0905 0 Td
(January)Tj
3.7205 0 Td
(18,)Tj
1.5804 0 Td
(2018)Tj
23.6269 0 Td
(3)Tj
0.7654 0 Td
(/)Tj
ET
endstream
endobj
58 0 obj
<>stream
endstream
endobj
59 0 obj
<>stream
endstream
endobj
60 0 obj
<>stream
endstream
endobj
61 0 obj
<>stream
endstream
endobj
62 0 obj
<>stream
endstream
endobj
63 0 obj
<>stream
endstream
endobj
64 0 obj
<>stream
endstream
endobj
65 0 obj
<>stream
endstream
endobj
66 0 obj
<>stream
endstream
endobj
67 0 obj
<>stream
endstream
endobj
68 0 obj
<>stream
endstream
endobj
69 0 obj
<>stream
endstream
endobj
70 0 obj
<>stream
endstream
endobj
71 0 obj
<>stream
endstream
endobj
72 0 obj
<>stream
endstream
endobj
73 0 obj
<>stream
BT
66.402 0 Td
(15)Tj
ET
Q
endstream
endobj
74 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 12 0 R/Annots 76 0 R/Contents 77 0 R/TrimBox[0 0 612 792]>>
endobj
76 0 obj
[78 0 R]
endobj
78 0 obj
<>/Border[0 0 0]/A 79 0 R>>
endobj
79 0 obj
<>
endobj
77 0 obj
[80 0 R 81 0 R 82 0 R 83 0 R 84 0 R]
endobj
80 0 obj
<>stream
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 706.0535 cm
BT
/F11 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Study)Tj
2.6173 0 Td
(population)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 689.1023 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Adults)Tj
2.8573 0 Td
(age)Tj
1.5363 0 Td
(between)Tj
3.5206 0 Td
(18)Tj
1.1679 0 Td
(and)Tj
1.7235 0 Td
(45)Tj
1.1678 0 Td
(years)Tj
2.2564 0 Td
(and)Tj
1.7234 0 Td
(weighting)Tj
4.1613 0 Td
(up)Tj
1.2585 0 Td
(to)Tj
1.0205 0 Td
(75)Tj
1.1622 0 Td
(Kg)Tj
1.355 0 Td
(with)Tj
1.9899 0 Td
(no)Tj
1.2699 0 Td
(known)Tj
2.999 0 Td
(chronic)Tj
3.2825 0 Td
(medical)Tj
-34.452 -1.3039 Td
(conditions)Tj
4.473 0 Td
(and)Tj
1.7291 0 Td
(a)Tj
0.6576 0 Td
(normal)Tj
3.1465 0 Td
(physical)Tj
3.4526 0 Td
(exam)Tj
2.3584 0 Td
(were)Tj
2.1259 0 Td
(recruited)Tj
3.8551 0 Td
(for)Tj
1.3833 0 Td
(participation.)Tj
5.5956 0 Td
(Female)Tj
3.0954 0 Td
(volunteers)Tj
-31.8725 -1.2982 Td
(had)Tj
1.7064 0 Td
(to)Tj
1.0261 0 Td
(use)Tj
1.5307 0 Td
(reliable)Tj
3.1408 0 Td
(contraceptive)Tj
5.6126 0 Td
(measures)Tj
3.9401 0 Td
(to)Tj
1.0261 0 Td
(be)Tj
1.1509 0 Td
(eligible)Tj
3.0614 0 Td
(to)Tj
1.0261 0 Td
(participate.)Tj
4.6998 0 Td
(Exclusion)Tj
4.1329 0 Td
(criteria)Tj
3.0784 0 Td
(were:)Tj
-35.1323 -1.2983 Td
(Intake)Tj
2.7609 0 Td
(of)Tj
1.0148 0 Td
(ABZ)Tj
2.0863 0 Td
(or)Tj
1.0941 0 Td
(other)Tj
2.3471 0 Td
(BZD)Tj
2.1373 0 Td
(drugs)Tj
2.4775 0 Td
(within)Tj
2.8119 0 Td
(the)Tj
1.4684 0 Td
(last)Tj
1.559 0 Td
(30)Tj
1.1735 0 Td
(days;)Tj
2.2224 0 Td
(malabsorption)Tj
6.0377 0 Td
(or)Tj
1.0942 0 Td
(other)Tj
2.3528 0 Td
(syndromes)Tj
-32.6379 -1.3039 Td
(that)Tj
1.7744 0 Td
(could)Tj
2.4548 0 Td
(compromise)Tj
5.2384 0 Td
(the)Tj
1.4683 0 Td
(tolerability)Tj
4.5411 0 Td
(or)Tj
1.0999 0 Td
(absorption)Tj
4.5354 0 Td
(of)Tj
1.0148 0 Td
(ABZ;)Tj
2.313 0 Td
(history)Tj
3.0047 0 Td
(of)Tj
1.0148 0 Td
(hypersensitivity)Tj
6.514 0 Td
(or)Tj
-34.9736 -1.2983 Td
(intolerance)Tj
4.7111 0 Td
(to)Tj
1.0261 0 Td
(ABZ)Tj
2.0807 0 Td
(or)Tj
1.0998 0 Td
(its)Tj
1.1452 0 Td
(inactive)Tj
3.3392 0 Td
(ingredients;)Tj
4.9492 0 Td
(acute)Tj
2.3244 0 Td
(clinical)Tj
3.0784 0 Td
(condition;)Tj
4.337 0 Td
(pregnancy)Tj
4.4107 0 Td
(or)Tj
1.0942 0 Td
(breast)Tj
-33.596 -1.2982 Td
(feeding.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 582.0661 cm
BT
/F11 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Chemicals)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 565.0582 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Pure)Tj
2.0976 0 Td
(reference)Tj
3.9174 0 Td
(standards)Tj
4.0876 0 Td
(of)Tj
1.0148 0 Td
(ABZ,)Tj
2.3073 0 Td
(ABZSO,)Tj
3.532 0 Td
(ABZSO)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 400.4787 563.4141 cm
BT
/F6 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(2)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 406.2047 565.0582 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(and)Tj
1.7347 0 Td
(oxibendazole)Tj
5.4879 0 Td
(\(OBZ\))Tj
2.8289 0 Td
(\(99%)Tj
2.2677 0 Td
(purity\))Tj
-32.9382 -1.2982 Td
(were)Tj
2.1203 0 Td
(purchased)Tj
4.3369 0 Td
(from)Tj
2.2054 0 Td
(SigmaAldrich)Tj
6.2475 0 Td
(\(St.)Tj
1.5591 0 Td
(Louis,)Tj
2.6418 0 Td
(MO,)Tj
2.0862 0 Td
(USA\).)Tj
2.6816 0 Td
(The)Tj
1.7801 0 Td
(HPLC)Tj
2.7496 0 Td
(grade)Tj
2.4435 0 Td
(solvents)Tj
3.4185 0 Td
(acetoni-)Tj
-34.2705 -1.3039 Td
(trile)Tj
1.8255 0 Td
(and)Tj
1.7291 0 Td
(methanol)Tj
4.0252 0 Td
(were)Tj
2.1259 0 Td
(from)Tj
2.2054 0 Td
(Baker,)Tj
2.7496 0 Td
(Mallinckrodt)Tj
5.4765 0 Td
(\(Baker,)Tj
3.0896 0 Td
(Phillipsburg,)Tj
5.3121 0 Td
(USA\).)Tj
2.6816 0 Td
(Ethyl)Tj
2.313 0 Td
(acetate)Tj
-33.5335 -1.2983 Td
(was)Tj
1.6951 0 Td
(from)Tj
2.211 0 Td
(Anedra)Tj
3.2088 0 Td
(\(BA,)Tj
2.0466 0 Td
(Argentina\).)Tj
4.8245 0 Td
(Water)Tj
2.7156 0 Td
(was)Tj
1.7008 0 Td
(distilled)Tj
3.3844 0 Td
(and)Tj
1.7291 0 Td
(deionized)Tj
4.1273 0 Td
(using)Tj
2.3867 0 Td
(a)Tj
0.652 0 Td
(water)Tj
2.4321 0 Td
(purifica-)Tj
-33.114 -1.2983 Td
(tion)Tj
1.8425 0 Td
(system)Tj
2.9366 0 Td
(\(Simplicity,)Tj
4.8189 0 Td
(Millipore,)Tj
4.1839 0 Td
(S)Tj
/F12 1 Tf
[()]TJ
/F6 1 Tf
(o)Tj
1.6384 0 Td
(Paulo,)Tj
2.7213 0 Td
(Brazil\).)Tj
3.0953 0 Td
(ABZ)Tj
2.0863 0 Td
(tabs)Tj
1.8198 0 Td
(\(400mg\))Tj
3.6113 0 Td
(administered)Tj
5.4879 0 Td
(to)Tj
-34.2422 -1.3039 Td
(human)Tj
3.0784 0 Td
(volunteers)Tj
4.3823 0 Td
(was)Tj
1.6951 0 Td
(provided)Tj
3.8154 0 Td
(by)Tj
1.1849 0 Td
(GlaxoSmithKline.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 471.0047 cm
BT
/F11 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Experimental)Tj
5.863 0 Td
(design)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 454.0535 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Eight)Tj
2.347 0 Td
(\(8\))Tj
1.3777 0 Td
(healthy)Tj
3.1294 0 Td
(volunteers)Tj
4.3823 0 Td
(\(four)Tj
2.2564 0 Td
(male)Tj
2.143 0 Td
(and)Tj
1.7291 0 Td
(four)Tj
1.9105 0 Td
(female,)Tj
3.0841 0 Td
(1840)Tj
2.6362 0 Td
(years)Tj
2.2677 0 Td
(of)Tj
1.0148 0 Td
(age;)Tj
1.7688 0 Td
(body)Tj
2.2167 0 Td
(weight)Tj
-32.2637 -1.3039 Td
(between)Tj
3.5262 0 Td
(53)Tj
1.1736 0 Td
(and)Tj
1.7291 0 Td
(75)Tj
1.1735 0 Td
(kg\))Tj
1.5194 0 Td
(participated)Tj
5.0003 0 Td
(in)Tj
1.0374 0 Td
(the)Tj
1.4684 0 Td
(trial.)Tj
2.0636 0 Td
(The)Tj
1.7801 0 Td
(treatment)Tj
4.1329 0 Td
(and)Tj
1.7348 0 Td
(sampling)Tj
3.8778 0 Td
(phases)Tj
2.8459 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
-34.0778 -1.2982 Td
(study)Tj
2.3867 0 Td
(were)Tj
2.126 0 Td
(conducted)Tj
4.4277 0 Td
(at)Tj
0.9524 0 Td
(the)Tj
1.4683 0 Td
(Laboratory)Tj
4.6432 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(Instituto)Tj
4.0592 0 Td
(de)Tj
1.1678 0 Td
(Investigaciones)Tj
6.3439 0 Td
(en)Tj
1.1963 0 Td
(Enfermedades)Tj
-31.2546 -1.2983 Td
(Tropicales)Tj
4.7735 0 Td
(at)Tj
0.9524 0 Td
(the)Tj
1.4683 0 Td
(Oran)Tj
2.3188 0 Td
(branch)Tj
3.033 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(Universidad)Tj
5.1421 0 Td
(Nacional)Tj
3.8154 0 Td
(de)Tj
1.1735 0 Td
(Salta,)Tj
2.3301 0 Td
(Argentina.)Tj
-26.294 -1.3039 Td
(Prior)Tj
2.296 0 Td
(to)Tj
1.0261 0 Td
(ABZ)Tj
2.0863 0 Td
(treatment,)Tj
4.3597 0 Td
(all)Tj
1.1452 0 Td
(subjects)Tj
3.3789 0 Td
(were)Tj
2.1259 0 Td
(provided)Tj
3.8154 0 Td
(with)Tj
1.9956 0 Td
(a)Tj
0.6576 0 Td
(standard)Tj
3.7191 0 Td
(meal)Tj
2.143 0 Td
(\(fat)Tj
1.5817 0 Td
(content)Tj
3.2655 0 Td
(40)Tj
1.1735 0 Td
(g\))Tj
-35.9657 -1.2983 Td
(and)Tj
1.7291 0 Td
(baseline)Tj
3.4299 0 Td
(blood)Tj
2.5171 0 Td
(\(5)Tj
1.0318 0 Td
(mL\))Tj
1.9219 0 Td
(and)Tj
1.7291 0 Td
(urine)Tj
2.3584 0 Td
(\(20)Tj
1.5081 0 Td
(mL\))Tj
1.9218 0 Td
(samples)Tj
3.3789 0 Td
(were)Tj
2.126 0 Td
(obtained)Tj
3.7304 0 Td
(\(sampling)Tj
4.2179 0 Td
(time)Tj
2.0296 0 Td
(=)Tj
0.7993 0 Td
(0\).)Tj
-34.4293 -1.2982 Td
(After)Tj
2.2847 0 Td
(15)Tj
1.1678 0 Td
(min)Tj
1.8595 0 Td
(a)Tj
0.652 0 Td
(single)Tj
2.5342 0 Td
(postprandial)Tj
5.2497 0 Td
(\(fat)Tj
1.576 0 Td
(content)Tj
3.2712 0 Td
(40)Tj
1.1679 0 Td
(g\))Tj
1.0261 0 Td
(oral)Tj
1.7802 0 Td
(dose)Tj
2.0409 0 Td
(of)Tj
1.0148 0 Td
(ABZ)Tj
2.0806 0 Td
(\(400)Tj
1.9899 0 Td
(mg\))Tj
1.8425 0 Td
(was)Tj
1.7008 0 Td
(adminis-)Tj
-33.2388 -1.304 Td
(tered)Tj
2.262 0 Td
(and)Tj
1.7291 0 Td
(consecutive)Tj
4.8812 0 Td
(venous)Tj
3.0444 0 Td
(blood)Tj
2.5115 0 Td
(samples)Tj
3.3846 0 Td
(were)Tj
2.1203 0 Td
(collected)Tj
3.7417 0 Td
(by)Tj
1.1792 0 Td
(a)Tj
0.6576 0 Td
(registered)Tj
4.1499 0 Td
(nurse)Tj
2.4548 0 Td
(at)Tj
0.9524 0 Td
(2,)Tj
0.9184 0 Td
(4,)Tj
0.9185 0 Td
(8,)Tj
0.924 0 Td
(12,)Tj
-35.8296 -1.2982 Td
(24,)Tj
1.3946 0 Td
(36,)Tj
1.3946 0 Td
(48)Tj
1.1736 0 Td
(and)Tj
1.7291 0 Td
(72)Tj
1.1735 0 Td
(h)Tj
0.7484 0 Td
(post-treatment)Tj
6.1681 0 Td
(\(p.t.\).)Tj
2.3924 0 Td
(Blood)Tj
2.5852 0 Td
(was)Tj
1.7008 0 Td
(collected)Tj
3.7417 0 Td
(into)Tj
1.8368 0 Td
(tubes)Tj
2.3414 0 Td
(and)Tj
1.7292 0 Td
(centrifuged)Tj
4.7848 0 Td
(imme-)Tj
-34.8942 -1.2983 Td
(diately.)Tj
3.0954 0 Td
(Serum)Tj
2.8403 0 Td
(samples)Tj
3.3788 0 Td
(were)Tj
2.126 0 Td
(stored)Tj
2.7042 0 Td
(at)Tj
/F12 1 Tf
0.9525 0 Td
[()]TJ
/F6 1 Tf
(70C)Tj
2.8006 0 Td
(until)Tj
2.109 0 Td
(assayed.)Tj
3.4355 0 Td
(Urine)Tj
2.5682 0 Td
(samples)Tj
3.3845 0 Td
(were)Tj
2.1203 0 Td
(collected)Tj
3.7418 0 Td
(at)Tj
0.9524 0 Td
(the)Tj
-36.2095 -1.3039 Td
(following)Tj
3.9798 0 Td
(specific)Tj
3.1918 0 Td
(times:)Tj
2.6135 0 Td
(4,)Tj
0.9184 0 Td
(8,)Tj
0.9241 0 Td
(12,)Tj
1.3946 0 Td
(24,)Tj
1.3947 0 Td
(36,)Tj
1.4003 0 Td
(48)Tj
1.1678 0 Td
(and)Tj
1.7348 0 Td
(72)Tj
1.1679 0 Td
(h.)Tj
0.9751 0 Td
(Samples)Tj
3.4979 0 Td
(were)Tj
2.1203 0 Td
(stored)Tj
2.7099 0 Td
(at)Tj
0.9525 0 Td
(-20C)Tj
2.5738 0 Td
(until)Tj
2.109 0 Td
(HPLC)Tj
-34.8262 -1.2983 Td
(analysis)Tj
3.3278 0 Td
(of)Tj
1.0148 0 Td
(ABZ/metabolites.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 281.9905 cm
BT
/F11 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Chromatographic)Tj
7.6819 0 Td
(analysis)Tj
3.5055 0 Td
(of)Tj
1.0678 0 Td
(ABZ/metabolites)Tj
7.3276 0 Td
(in)Tj
1.0677 0 Td
(collected)Tj
3.893 0 Td
(samples)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 211.9748 264.9826 cm
BT
/F11 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Serum)Tj
2.9423 0 Td
(samples)Tj
3.5489 0 Td
(extraction.)Tj
/F6 1 Tf
5.2951 0 Td
(Serum)Tj
2.8347 0 Td
(samples)Tj
3.3845 0 Td
(\(1)Tj
1.0375 0 Td
(mL\))Tj
1.9162 0 Td
(were)Tj
2.1203 0 Td
(placed)Tj
2.7949 0 Td
(into)Tj
1.8425 0 Td
(plastic)Tj
2.7666 0 Td
(tubes)Tj
2.3358 0 Td
(\(5)Tj
1.0374 0 Td
(mL\).)Tj
-35.0529 -1.2982 Td
(The)Tj
1.7801 0 Td
(samples)Tj
3.3845 0 Td
(were)Tj
2.1203 0 Td
(spiked)Tj
2.812 0 Td
(with)Tj
2.0012 0 Td
(40)Tj
/F12 1 Tf
1.1679 0 Td
[()]TJ
/F6 1 Tf
(L)Tj
1.2642 0 Td
(of)Tj
1.0148 0 Td
(OBZ-IS)Tj
3.3166 0 Td
(\(25)Tj
/F12 1 Tf
1.5136 0 Td
[()]TJ
/F6 1 Tf
(g/mL\))Tj
3.2145 0 Td
(and)Tj
1.7348 0 Td
(the)Tj
1.4683 0 Td
(molecules)Tj
4.1953 0 Td
(to)Tj
1.0261 0 Td
(be)Tj
1.1509 0 Td
(assayed)Tj
-33.1651 -1.2983 Td
(\(ABZ,)Tj
2.6475 0 Td
(ABZSO,)Tj
3.5319 0 Td
(ABZSO)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 292.7055 237.3165 cm
BT
/F6 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(2)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 296.2771 239.0173 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(\))Tj
0.5555 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(validation)Tj
4.2066 0 Td
(procedure.)Tj
4.5354 0 Td
(Drug)Tj
2.3244 0 Td
(molecules)Tj
4.1953 0 Td
(were)Tj
2.126 0 Td
(extracted)Tj
3.8834 0 Td
(from)Tj
-33.9587 -1.3039 Td
(serum)Tj
2.7212 0 Td
(by)Tj
1.1849 0 Td
(a)Tj
0.6519 0 Td
(solid)Tj
2.126 0 Td
(phase)Tj
2.4831 0 Td
(extraction)Tj
4.2576 0 Td
(\(SPE\))Tj
2.5058 0 Td
(procedure.)Tj
4.541 0 Td
(SPE)Tj
1.8199 0 Td
(was)Tj
1.7007 0 Td
(made)Tj
2.4265 0 Td
(using)Tj
2.3867 0 Td
(C)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 494.7023 224.3338 cm
BT
/F6 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(18)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 504 225.9779 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(cartridges)Tj
4.1669 0 Td
(\(Strata,)Tj
-34.5654 -1.2982 Td
(RP-18)Tj
2.6986 0 Td
(100)Tj
1.6497 0 Td
(mg,)Tj
1.7291 0 Td
(Phenomenex,)Tj
5.692 0 Td
(CA,)Tj
1.7915 0 Td
(USA\))Tj
2.4604 0 Td
(previously)Tj
4.3483 0 Td
(conditioned)Tj
5.0684 0 Td
(with)Tj
1.9955 0 Td
(1)Tj
0.6973 0 Td
(mL)Tj
1.5761 0 Td
(of)Tj
1.0147 0 Td
(methanol,)Tj
4.2519 0 Td
(fol-)Tj
-34.9735 -1.2983 Td
(lowed)Tj
2.6079 0 Td
(by)Tj
1.1792 0 Td
(1)Tj
0.6973 0 Td
(mL)Tj
1.576 0 Td
(of)Tj
1.0148 0 Td
(water.)Tj
2.6589 0 Td
(The)Tj
1.7802 0 Td
(sample)Tj
3.0217 0 Td
(was)Tj
1.7007 0 Td
(applied)Tj
3.1522 0 Td
(and)Tj
1.7291 0 Td
(then)Tj
2.0182 0 Td
(sequentially)Tj
4.9606 0 Td
(washed)Tj
3.1747 0 Td
(with)Tj
2.0013 0 Td
(3)Tj
0.6916 0 Td
(mL)Tj
1.5817 0 Td
(of)Tj
-35.5461 -1.3039 Td
(HPLC)Tj
2.7496 0 Td
(water,)Tj
2.6532 0 Td
(dried)Tj
2.3357 0 Td
(with)Tj
2.0013 0 Td
(air)Tj
1.2926 0 Td
(for)Tj
1.3833 0 Td
(5)Tj
0.6973 0 Td
(min)Tj
1.8538 0 Td
(and)Tj
1.7292 0 Td
(eluted)Tj
2.6702 0 Td
(with)Tj
1.9956 0 Td
(2)Tj
0.6973 0 Td
(mL)Tj
1.576 0 Td
(of)Tj
1.0148 0 Td
(methanol.)Tj
4.252 0 Td
(The)Tj
1.78 0 Td
(elute)Tj
2.143 0 Td
(was)Tj
1.6951 0 Td
(evapo-)Tj
-34.52 -1.2983 Td
(rated)Tj
2.2734 0 Td
(to)Tj
1.0261 0 Td
(dryness)Tj
3.2655 0 Td
(under)Tj
2.6192 0 Td
(a)Tj
0.6576 0 Td
(gentle)Tj
2.6249 0 Td
(stream)Tj
2.9253 0 Td
(of)Tj
1.0148 0 Td
(nitrogen)Tj
3.651 0 Td
(at)Tj
0.9525 0 Td
(56C)Tj
2.228 0 Td
(in)Tj
1.0318 0 Td
(a)Tj
0.6576 0 Td
(water)Tj
2.4321 0 Td
(bath)Tj
1.9843 0 Td
(\(Zymark)Tj
3.7359 0 Td
(TurboVap)Tj
-33.08 -1.2982 Td
(LV)Tj
1.4513 0 Td
(evaporator.)Tj
4.7622 0 Td
(American)Tj
4.1953 0 Td
(Laboratory)Tj
4.6431 0 Td
(Trading,)Tj
3.668 0 Td
(Inc.)Tj
1.7575 0 Td
(Lyme)Tj
2.4547 0 Td
(06333)Tj
2.6022 0 Td
(CT)Tj
1.491 0 Td
(USA\).)Tj
2.6816 0 Td
(The)Tj
1.7857 0 Td
(dry)Tj
1.5704 0 Td
(residue)Tj
-33.063 -1.2983 Td
(was)Tj
1.6951 0 Td
(dissolved)Tj
3.9005 0 Td
(in)Tj
1.0318 0 Td
(250)Tj
/F12 1 Tf
1.6497 0 Td
[()]TJ
/F6 1 Tf
(L)Tj
1.2643 0 Td
(of)Tj
1.0148 0 Td
(mobile)Tj
2.9877 0 Td
(phase)Tj
2.4831 0 Td
(\(acetonitrile:water)Tj
7.2906 0 Td
(,)Tj
0.4423 0 Td
(27:73\).)Tj
2.9139 0 Td
(An)Tj
1.4514 0 Td
(aliquot)Tj
3.0103 0 Td
(\(50)Tj
/F12 1 Tf
1.508 0 Td
[()]TJ
/F6 1 Tf
(L\))Tj
1.6044 0 Td
(of)Tj
1.0148 0 Td
(this)Tj
-35.2627 -1.3039 Td
(solution)Tj
3.4809 0 Td
(was)Tj
1.7008 0 Td
(injected)Tj
3.3902 0 Td
(in)Tj
1.0318 0 Td
(the)Tj
1.4684 0 Td
(chromatographic)Tj
7.1149 0 Td
(system.)Tj
/F11 1 Tf
-16.9908 -1.2983 Td
(Urine)Tj
2.6305 0 Td
(samples)Tj
3.549 0 Td
(extraction.)Tj
/F6 1 Tf
5.2951 0 Td
(Urine)Tj
2.5625 0 Td
(samples)Tj
3.3845 0 Td
(\(3)Tj
1.0375 0 Td
(mL\))Tj
1.9162 0 Td
(were)Tj
2.1203 0 Td
(placed)Tj
2.795 0 Td
(into)Tj
1.8425 0 Td
(plastic)Tj
2.7665 0 Td
(tubes)Tj
2.3357 0 Td
(\(10)Tj
1.5137 0 Td
(mL\).)Tj
-34.9452 -1.2982 Td
(The)Tj
1.7801 0 Td
(samples)Tj
3.3846 0 Td
(were)Tj
2.1203 0 Td
(spiked)Tj
2.8119 0 Td
(with)Tj
2.0013 0 Td
(60)Tj
/F12 1 Tf
[()]TJ
/F6 1 Tf
(L)Tj
2.2167 0 Td
(of)Tj
1.0148 0 Td
(OBZ-IS)Tj
3.3108 0 Td
(\(25)Tj
/F12 1 Tf
1.5137 0 Td
[()]TJ
/F6 1 Tf
(g/mL\))Tj
3.2201 0 Td
(and)Tj
1.7292 0 Td
(the)Tj
1.4683 0 Td
(molecules)Tj
4.2008 0 Td
(to)Tj
1.0205 0 Td
(be)Tj
1.1508 0 Td
(assayed)Tj
-32.9439 -1.304 Td
(\(ABZ,)Tj
2.6475 0 Td
(ABZSO,)Tj
3.532 0 Td
(ABZSO)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 292.7055 94.337 cm
BT
/F6 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(2)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 296.2771 95.9811 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(\))Tj
0.5555 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(validation)Tj
4.2066 0 Td
(procedure.)Tj
4.5354 0 Td
(Analytes)Tj
3.6737 0 Td
(were)Tj
2.1203 0 Td
(extracted)Tj
3.8891 0 Td
(by)Tj
1.1792 0 Td
(addition)Tj
3.6 0 Td
(of)Tj
1.0148 0 Td
(3)Tj
-36.9067 -1.2982 Td
(mL)Tj
1.576 0 Td
(of)Tj
1.0148 0 Td
(ethyl)Tj
2.1713 0 Td
(acetate.)Tj
3.1805 0 Td
(After)Tj
2.2846 0 Td
(shaking)Tj
3.3222 0 Td
(\(vortex)Tj
3.0784 0 Td
(50)Tj
1.1735 0 Td
(min\),)Tj
2.4208 0 Td
(and)Tj
1.7291 0 Td
(centrifugation)Tj
5.8847 0 Td
(\(2300)Tj
2.4661 0 Td
(g,)Tj
0.9071 0 Td
(15)Tj
1.1735 0 Td
(min,)Tj
2.0807 0 Td
(4C\),)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 183.2882 23.6976 re
W* n
q
183.2315 0 0 23.6409 36 741.3165 cm
q
/I0 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 449.1212 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Urinary)Tj
3.3874 0 Td
(excretion)Tj
4.2024 0 Td
(of)Tj
1.0417 0 Td
(ABZ/meta)Tj
4.3937 0 Td
(bolites)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
163.5591 34.9228 m
317.7071 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(Neglected)Tj
4.6417 0 Td
(Tropical)Tj
3.7135 0 Td
(Disease)Tj
3.5433 0 Td
(s)Tj
0.7158 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8197 0 Td
(1/journal.pn)Tj
5.1237 0 Td
(td.00059)Tj
3.8197 0 Td
(45)Tj
0 g
2.0905 0 Td
(January)Tj
3.7205 0 Td
(18,)Tj
1.5804 0 Td
(2018)Tj
23.6269 0 Td
(4)Tj
0.7654 0 Td
(/)Tj
ET
endstream
endobj
81 0 obj
<>stream
endstream
endobj
82 0 obj
<>stream
endstream
endobj
83 0 obj
<>stream
endstream
endobj
84 0 obj
<>stream
BT
66.402 0 Td
(15)Tj
ET
Q
endstream
endobj
85 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 12 0 R/Annots 87 0 R/Contents 88 0 R/TrimBox[0 0 612 792]>>
endobj
86 0 obj
<>
endobj
89 0 obj
<>stream
/CIDInit/ProcSet findresource begin
12 dict begin begincmap
/CMapName/Adobe-Identity-UCS def
/CIDSystemInfo<>def
/CMapType 2 def
1 begincodespacerange
<0000>
endcodespacerange
2 beginbfchar
<010C><03B2>
<0115><03BB>
endbfchar
endcmap
CMapName currentdict /CMap defineresource pop end end
endstream
endobj
90 0 obj
<>/FontDescriptor 91 0 R/DW 250/W[268[495] 277[502]]>>
endobj
91 0 obj
<>
endobj
92 0 obj
<>stream
cvt f6 fpgm2Msf bglyfۅ head' 6hhea1 $hmtx&O