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Tacrolimus Population Pharmacokinetic Models According to CYP3A5 / CYP3A4 / POR Genotypes in Chinese Han Renal Transplant Patients
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Tacrolimus Population Pharmacokinetic Models According to CYP3A5 / CYP3A4 / POR Genotypes in Chinese Han Renal Transplant Patients
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Journal Article
Tacrolimus Population Pharmacokinetic Models According to CYP3A5 / CYP3A4 / POR Genotypes in Chinese Han Renal Transplant Patients
2018
Overview
To develop a population pharmacokinetic (PK) model of tacrolimus in Chinese Han renal transplant population and establish the influence of different covariates (especially different CYP3A5/3A4/POR genotype) on PK properties.
Trough tacrolimus concentrations, clinical characteristics and CYP3A5/CYP3A4/POR genotypes were collected from 141 adult renal transplant recipients after transplantation. The population PK analysis was carried out using the nonlinear mixed-effect modeling software NONMEM version 3.4.2.
Tacrolimus PK profiles exhibited high interpatient variability. A two compartment model with first-order input and elimination described the tacrolimus PK profiles in the studied population. Among the genotypes, only CYP3A5 genotype was confirmed to have clinical significance.
Our final model confirmed that CYP3A5*3 plays a more significant role in tacrolimus PK and could affect the blood concentrations and CL/F (clearance rate/bioavailbility). This model is expected to help to improve individualized tacrolimus dosing.
Publisher
Future Medicine Ltd
Subject
/ Asian Continental Ancestry Group - genetics
/ Blood
/ Cytochrome P-450 CYP3A - genetics
/ Cytochrome P-450 Enzyme System - genetics
/ DNA
/ Female
/ Genotype
/ Humans
/ Immunosuppressive Agents - pharmacokinetics
/ Kidney Transplantation - methods
/ Male
/ Metabolic Clearance Rate - genetics
/ Patients
/ Polymorphism, Single Nucleotide - genetics
/ Software
