Tacrolimus pharmacokinetics in the early post-liver transplantation period and clinical applicability via Bayesian prediction

Autor: Nerea Leal, Andrés Valdivieso, Itziar Oteo, Mikel Gastaca, Jorge Ortiz de Urbina, Elena Suarez, Rosario Calvo, John C. Lukas
Rok vydání: 2012
Předmět:
Zdroj: European Journal of Clinical Pharmacology. 69:65-74
ISSN: 1432-1041
0031-6970
DOI: 10.1007/s00228-012-1300-z
Popis: To define and validate a pharmacokinetic (PK) model for tacrolimus (TAC) that includes patient pathophysiology and has clinical applicability in the first 2 weeks post-liver transplantation (PLT). Routine monitoring records [dose, trough levels (Cmin), demographics, biochemistry] from 75 patients treated with TAC (Prograf®) PLT were used to develop a population PK model (employing NONMEM®) testing for predictors of oral clearance (CL/F) according to bedside evidence and primarily with aspartate aminotransferase (AST), albumin (ALB), and hematocrit (HCT). Patients were catergorized into subgroups with above and below “normal” thresholds for AST (500 U/L), ALB (2.5 g/dL), and HCT (28 %), respectively. The model was validated with ten patients from the same period and 15 more recent patients. An empirical Bayes method was developed and applied to the prediction of individual profiles serving as a dose adjustment tool. The number of days PLT (Days PLT) was a key variable during the first 2 weeks, with a dichotomy in the mono-compartmental parameters for 0–3 Days PLT and 4–15 Days PLT. During 0–3 Days PLT, AST levels, indicative of allograft functionality (and TAC metabolism), were crucial predictors of elimination. Three groups were identified with the following clearances: CL/F0-3 = 8.93 L/h for AST ≥500 U/L and CL/F0-3 = 11.0 L/h for AST
Databáze: OpenAIRE
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