Open AccessEstimation of Tacrolimus Clearance in Saudi Adult Kidney Transplant Recipients
Author(s) -
Saeed Alqahtani,
Maha Alenazi,
Abdullah Alsultan,
Emad Alsarhani
Publication year - 2021
Publication title -
saudi journal of kidney diseases and transplantation/našrat amraḍ wa zira'aẗ al-kulaẗ
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.268
H-Index - 30
eISSN - 2320-3838
pISSN - 1319-2442
DOI - 10.4103/1319-2442.318511
Subject(s) - tacrolimus , medicine , pharmacokinetics , population , dosing , volume of distribution , renal function , transplantation , urology , pharmacology , environmental health
Tacrolimus is commonly used in adult kidney transplant patients. Only few studies have so far described the pharmacokinetics of tacrolimus in the Saudi population. Thus, the goal of this study is to determine the population pharmacokinetics of tacrolimus in Saudi adult kidney transplant recipients and to identify the factors that explain variability. We performed a retrospective chart review of adult patients who received oral tacrolimus at two centers. We developed the population pharmacokinetic models using Monolix 4.4. The factors screened for influence on these parameters were weight, age, gender, liver function tests, and creatinine clearance. The analysis included a total of 149 tacrolimus plasma concentrations from 139 patients. A one-compartment open model with linear absorption and elimination adequately described the data. The average parameter estimates for apparent clearance (CL/F) and apparent volume of distribution (V/F) were 9.1 L/h and 912 L, respectively. The interindividual variabilities (coefficients of variation) in CL/F and V/F were 20% and 18%, respectively. Aspartate aminotransferase was identified to be the main covariate that influences tacrolimus CL/F. In conclusion, the population pharmacokinetic model of tacrolimus was established and a significant covariate of the model was identified. These findings offer a rationale for the personalization of tacrolimus dosing regimens. Further studies are required to understand the factors that may influence the pharmacokinetics of tacrolimus and assist in drug dosage decisions.