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Influence of CYP3A5 and MDR1(ABCB1) polymorphisms on the pharmacokinetics of tacrolimus in Chinese renal transplant recipients.
Transplant Proc. 2010 Nov; 42(9):3455-8.TP

Abstract

The aims of this study were to investigate the influence of CYP3A5 and MDR1 genetic polymorphisms on tacrolimus pharmacokinetics in Chinese renal transplant recipients, so as to help rational administration in clinical practice. We calculated pharmacokinetic parameters of tacrolimus from blood concentrations in steady state at day 28. Polymerase chain reaction restriction fragment length polymorphisms were used for CYP3A5 and MDR1 analysis. The results showed that the dose-adjusted area under the concentration time curve (AUC(0-12)) and renal clearance showed a significant difference between CYP3A5*1 carriers and the CYP3A5*3/*3 genotype (P < .01). In the following study, a distinction was made between carriers of CYP3A5*1/ vs CYP3A5*3/*3 seeking to investigate the influence of the MDR13435T>C polymorphism on tacrolimus pharmacokinetics. MDR1 3435T>C polymorphism did not affect any tacrolimus pharmacokinetic parameter in either group. Renal transplant recipients who were CYP3A5*1 carriers required a higher dose of tacrolimus than CYP3A5*3/*3, indicating a significantly lower dose-adjusted AUC(0-12) of tacrolimus. In contrast, MDR1 3435T>C polymorphism was not an important factor in tacrolimus pharmacokinetics. Pharmacogenetic methods may be used prospectively to aid dose selection and individualize immunosuppressive therapy.

Authors+Show Affiliations

Organ Transplantation Institute of The Third Xiangya Hospital, Central South University, Changsha, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21094796

Citation

Rong, G, et al. "Influence of CYP3A5 and MDR1(ABCB1) Polymorphisms On the Pharmacokinetics of Tacrolimus in Chinese Renal Transplant Recipients." Transplantation Proceedings, vol. 42, no. 9, 2010, pp. 3455-8.
Rong G, Jing L, Deng-Qing L, et al. Influence of CYP3A5 and MDR1(ABCB1) polymorphisms on the pharmacokinetics of tacrolimus in Chinese renal transplant recipients. Transplant Proc. 2010;42(9):3455-8.
Rong, G., Jing, L., Deng-Qing, L., Hong-Shan, Z., Shai-Hong, Z., & Xin-Min, N. (2010). Influence of CYP3A5 and MDR1(ABCB1) polymorphisms on the pharmacokinetics of tacrolimus in Chinese renal transplant recipients. Transplantation Proceedings, 42(9), 3455-8. https://doi.org/10.1016/j.transproceed.2010.08.063
Rong G, et al. Influence of CYP3A5 and MDR1(ABCB1) Polymorphisms On the Pharmacokinetics of Tacrolimus in Chinese Renal Transplant Recipients. Transplant Proc. 2010;42(9):3455-8. PubMed PMID: 21094796.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Influence of CYP3A5 and MDR1(ABCB1) polymorphisms on the pharmacokinetics of tacrolimus in Chinese renal transplant recipients. AU - Rong,G, AU - Jing,L, AU - Deng-Qing,L, AU - Hong-Shan,Z, AU - Shai-Hong,Z, AU - Xin-Min,N, PY - 2009/07/22/received PY - 2010/07/02/revised PY - 2010/08/20/accepted PY - 2010/11/25/entrez PY - 2010/11/26/pubmed PY - 2011/3/8/medline SP - 3455 EP - 8 JF - Transplantation proceedings JO - Transplant Proc VL - 42 IS - 9 N2 - The aims of this study were to investigate the influence of CYP3A5 and MDR1 genetic polymorphisms on tacrolimus pharmacokinetics in Chinese renal transplant recipients, so as to help rational administration in clinical practice. We calculated pharmacokinetic parameters of tacrolimus from blood concentrations in steady state at day 28. Polymerase chain reaction restriction fragment length polymorphisms were used for CYP3A5 and MDR1 analysis. The results showed that the dose-adjusted area under the concentration time curve (AUC(0-12)) and renal clearance showed a significant difference between CYP3A5*1 carriers and the CYP3A5*3/*3 genotype (P < .01). In the following study, a distinction was made between carriers of CYP3A5*1/ vs CYP3A5*3/*3 seeking to investigate the influence of the MDR13435T>C polymorphism on tacrolimus pharmacokinetics. MDR1 3435T>C polymorphism did not affect any tacrolimus pharmacokinetic parameter in either group. Renal transplant recipients who were CYP3A5*1 carriers required a higher dose of tacrolimus than CYP3A5*3/*3, indicating a significantly lower dose-adjusted AUC(0-12) of tacrolimus. In contrast, MDR1 3435T>C polymorphism was not an important factor in tacrolimus pharmacokinetics. Pharmacogenetic methods may be used prospectively to aid dose selection and individualize immunosuppressive therapy. SN - 1873-2623 UR - https://www.unboundmedicine.com/medline/citation/21094796/Influence_of_CYP3A5_and_MDR1_ABCB1__polymorphisms_on_the_pharmacokinetics_of_tacrolimus_in_Chinese_renal_transplant_recipients_ DB - PRIME DP - Unbound Medicine ER -