Artículo
Population pharmacokinetics of sublingually administered tacrolimus in infants and young children with liver transplantation
Riva, Natalia
; Ibarra, Manuel; Parra Guillen, Zinnia P.; Galván, Maria Eugenia; Pérez, Erika; Trezeguet Renatti, Guido
; Cáceres Guido, Paulo; Lopez, Clarisa; Licciardone, Nieves; Halac, Esteban Tomas; Dip, Marcelo Fabian; Cruz, Alejandro; Imventarza, Oscar Cesar; Buamscha, Daniel; Troconiz, Iñaki F.; Schaiquevich, Paula Susana
Fecha de publicación:
03/2023
Editorial:
Wiley Blackwell Publishing, Inc
Revista:
British Journal Of Clinical Pharmacology
ISSN:
0306-5251
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Aims: Pharmacokinetics of tacrolimus after sublingual administration is not characterized in paediatric liver transplant patients. Therefore, we aimed to develop a population pharmacokinetic model of sublingually administered tacrolimus in patients who cannot swallow the capsules due to their age, sedation status and/or mechanical ventilation during the first weeks post-transplantation. Methods: Demographic, clinical and pharmacological variables, including tacrolimus whole blood concentrations obtained from therapeutic drug monitoring and data from dense-sampling pharmacokinetic profiles, were recorded in 26 paediatric patients with biliary atresia who underwent liver transplantation between 2016 and 2021. Population pharmacokinetic analysis was performed with NONMEM v7.4. Results: Disposition of tacrolimus was best characterized by a 2-compartment model with clearance achieving half of the maximum elimination capacity (CLMAX = 4.1 L/h) at 4.6 days post-transplantation (T50). Compared to sedated patients, nonsedated status showed an increased first-order absorption rate constant (1.1 vs. 0.1 h−1) and a 24% reduction in bioavailability (FNS) at 14 days post-transplant. The model was able to explain the oral absorption pattern in nonsedated patients as the result of gut bioavailability (0.9) and hepatic extraction ratio, with the latter being responsible for first-pass effects. Estimates of interindividual variability remained moderate (25.9% for the gut bioavailability) to high (79.8% for the apparent volume of distribution of the central compartment, and 101% for T50). Conclusion: A population pharmacokinetic model of sublingually administered tacrolimus in paediatric patients was developed to characterize different absorption mechanisms. Once the model is externally validated, the effect of post-transplant time on clearance and the sedation status may be considered in routine dosing management.
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Identificadores
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Articulos(SEDE CENTRAL)
Articulos de SEDE CENTRAL
Articulos de SEDE CENTRAL
Citación
Riva, Natalia; Ibarra, Manuel; Parra Guillen, Zinnia P.; Galván, Maria Eugenia; Pérez, Erika; et al.; Population pharmacokinetics of sublingually administered tacrolimus in infants and young children with liver transplantation; Wiley Blackwell Publishing, Inc; British Journal Of Clinical Pharmacology; 89; 3; 3-2023; 1115-1126
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