Initial dosage optimization of tacrolimus in Chinese pediatric patients undergoing kidney transplantation based on population pharmacokinetics and pharmacogenetics.

Abstract

BACKGROUND:

The purpose of our research was to recommend the initial tacrolimus dosage for Chinese pediatric patients undergoing kidney transplantation based on population pharmacokinetics and pharmacogenetics.

METHODS:

Demographic data, laboratory results, drug combinations, and pharmacogenetics from Chinese pediatric patients undergoing kidney transplantation were analyzed using non-linear mixed-effects modeling. A Monte Carlo simulation was performed to evaluate the optimal initial dose of tacrolimus.

RESULTS:

Body weight and post-transplant days, combined with wuzhi-capsule (WZ, extracted from schisandra sphenanthera, whose primary efficient constituents are schisantherin A, schisandrol B, schisandrin, etc., and often used to treat drug-induced hepatitis in Chinese organ transplant patients) and CYP3A5 polymorphisms, influenced the clearance of tacrolimus in these patients. With same weight and post-transplant days, tacrolimus clearance rates from patients carrying CYP3A5*3/*3 and without WZ, carrying CYP3A5*1 allele and without WZ, carrying CYP3A5*3/*3 and with WZ, carrying CYP3A5*1 allele and with WZ were 1, 1.6, 0.72, and 1.152, respectively. In addition, the initial dose for each condition is recommended.

CONCLUSIONS:

The initial dosage recommendations in the tacrolimus instructions were not individualized, and we have developed more accurate initial doses based on weight and the CYP3A5 genotype. In addition, lower initial doses are recommended with concurrent use of WZ.

• Authors: Xiao Chen, Dong-Dong Wang, Hong Xu, Zhi-Ping Li
• Journal: Expert review of clinical pharmacology (Expert Rev Clin Pharmacol) Vol. 13 Issue 5 Pg. 553-561 (May 2020) ISSN: 1751-2441 [Electronic] England
• PMID: 32452705 (Publication Type: Journal Article)

Chemical References

• Drugs, Chinese Herbal
• Immunosuppressive Agents
• wuzhi
• CYP3A5 protein, human
• Cytochrome P-450 CYP3A
• Tacrolimus

Topics

• Adolescent
• Asian People
• Child
• Child, Preschool
• Cytochrome P-450 CYP3A (genetics)
• Dose-Response Relationship, Drug
• Drugs, Chinese Herbal (administration & dosage)
• Female
• Genotype
• Humans
• Immunosuppressive Agents (administration & dosage, pharmacokinetics)
• Kidney Transplantation
• Male
• Models, Biological
• Monte Carlo Method
• Pharmacogenetics
• Retrospective Studies
• Tacrolimus (administration & dosage, pharmacokinetics)