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2000
Volume 22, Issue 10
  • ISSN: 1389-2002
  • E-ISSN: 1875-5453

Abstract

Background: Although the pharmacokinetic variability of Tacrolimus (Tac) metabolism is primarily influenced by CYP3A5 genotypes, the potential effect according to CYP3A5 polymorphisms in Tac extended-release (Tac-ER) and immediate-release (Tac-IR) and between these formulations’ conversion needs further investigation. The purpose of this study was to clarify the association of CYP3A5 genotypes and pharmacokinetics of different Tac formulations in renal transplant recipients. Methods: PubMed, EMBASE, and Cochrane Library databases were searched for eligible studies (protocol registration No. CRD 42019133790 in PROSPERO network). The summary weighted mean difference with 95% confidence intervals was calculated for pharmacokinetic parameters using the random-effects model according to posttransplantation periods, genotypes and formulations. Sensitivity analysis, publication bias, and subgroup analyses were conducted. Results: A total of 27 studies involving 2,713 renal transplant recipients were adopted. Whether patients treated with Tac-ER or Tac-IR, CYP3A5 non-expressors (*3/*3) had a decreased daily dose and CL/F, an increased C, C/D, AUC/D and C/D than expressors (*1/*1 or *1/*3) at most post-transplantation periods. Furthermore, when 1:1 dose conversion from Tac-IR to Tac-ER (all at ≥12 months post-transplantation), C and C were decreased in both CYP3A5 non-expressors and expressors, while daily dose was only decreased in CYP3A5 nonexpressors and AUC was only decreased in CYP3A5 expressors. Finally, subgroup analyses indicated that ethnicity, mean age, and male percentage influenced daily dose and C of Tac, especially for Tac-IR. Conclusion: The results indicated that CYP3A5 genotypes affect the pharmacokinetics of Tac in renal transplant recipients in both formulations and between formulations’ conversion. Future studies should be exploring more other associations of CYP3A5 genotypes and the pharmacodynamics of Tac.

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/content/journals/cdm/10.2174/1389200222666210825160021
2021-08-01
2025-07-12
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