Utility of the micro-blood sampling (drug blood spot) technique for pharmacokinetic studies

Abstract

Introduction: Typical pharmacokinetic (PK) studies require the collection of blood samples over time, which are commonly obtained by venous puncture. The recovered serum or plasma needs to be conserved at -18°C until analysed. This is a complication in field studies where samples are obtained far away to the analytical laboratory. Micro-blood sampling such as the dried blood spot (DBS) technique offers an alternative for PK studies both in animals and humans. DBS do not require cooling or freezing, which makes easier to send blood samples to remote sites (long distances or even for material needed to be exchanged between different countries). However, the DBS technique has not yet been validated for drug quantification in livestock animals. This validation procedure was carried out in the framework of a study aimed to evaluate the impact of feeding management on the plasma disposition kinetics of albendazole (ABZ) in pigs. The current work had two main goals: 1) to validate a DBS technique as a useful tool to characterize drug PK and, 2) to investigate the impact of feeding on the PK behaviour of ABZ in pigs. Methods: Twelve (12) crossbred pigs were randomly allocated into two groups: Group A: animals were fasted during 8 h prior to ABZ treatment. Group B: pigs were fed ad libitum with a commercial flour-balanced complete food. Both groups were orally treated with ABZ at 10 mg/kg. Blood samples were taken between 0 and 48 h post-treatment. At each sampling point, blood was either dropped (70 µL) onto DBS cards or conventionally centrifuged to obtain plasma. Then, both the DBS cards and the collected plasma samples were subjected to different extraction procedures and analyzed by HPLC to quantify ABZ and its metabolites. Results: Equivalent concentration-time profiles were obtained after drug extraction from both matrices (DBS and plasma). ABZ sulphoxide (ABZSO), the main systemically measurable ABZ metabolite, showed similar PK behaviour in both cases. In addition, similar (P> 0.05) plasma drug exposure was obtained for ABZSO in both experimental groups (fasted and fed), with AUC values of 32.5 ± 5.05 µg.h/mL (fasted) and 27.4 ± 6.16 µg.h/mL (fed). The peak concentrations in plasma were also similar (P> 0.05) in fasted and fed groups. Conclusions: The DBS demonstrated to be a practical and reliable technique for PK studies in animals. Under our experimental conditions, fasting before ABZ administration did not significantly modify the plasma disposition kinetics of ABZSO in pigs.