Population pharmacokinetics and dosing regimen optimization of tacrolimus in Chinese lung transplant recipients.

Population pharmacokinetics and dosing regimen optimization of tacrolimus in Chinese lung transplant recipients. Eur J Pharm Sci. 2020 Jul 01;:105448 Authors: Cai X, Song H, Jiao Z, Yang H, Zhu M, Wang C, Wei D, Shi L, Wu B, Chen J Abstract We aimed to (i) develop a population pharmacokinetic model of tacrolimus in Chinese lung transplant recipients and (ii) propose model-based dosing regimens for individualized treatment. We obtained 807 tacrolimus steady-state whole blood concentrations from 52 lung transplant patients and genotyped CYP3A5*3. Population pharmacokinetic analysis was performed using nonlinear mixed-effects modeling. Monte Carlo simulations were employed to determine the initial dosing regimens. Tacrolimus pharmacokinetics was described by a one-compartment model with first-order absorption and elimination processes. In CYP3A5*3/*3 70-kg patients with 30% hematocrit and voriconazole-free therapy, the mean estimated apparent clearance was 13.1 l h-1 with 20.1% between-subject variability, which was lower than that in Caucasian lung transplant patients (17.5-36.5 l h-1). Hematocrit, postoperative days, tacrolimus daily dose, voriconazole concomitant therapy, and CYP3A5*3 genotype were identified as significant covariates for tacrolimus clearance. To achieve target trough concentration (10-15 ng ml-1) on the 8th day post-transplant, a higher initial dosage than the current regimen of 0.04 mg kg-1 every 12 hours is recomm...
Source: European Journal of Pharmaceutical Sciences - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharm Sci Source Type: research