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CYP3A5*3 genotype associated with intrasubject pharmacokinetic variation toward tacrolimus in bioequivalence study.
Ther Drug Monit. 2010 Feb; 32(1):67-72.TD

Abstract

Tacrolimus is metabolized by CYP3A and has highly variable pharmacokinetics. To study the factors contributing to this high variability in pharmacokinetics and to investigate the possibility of genotype-specific clinical applications, the effect of differing CYP3A5 genotypes on the intrasubject coefficients of variation for tacrolimus was investigated. Genotyping for CYP3A5*3 was performed in healthy volunteers who had previously participated in the pharmacokinetic study of 2 tacrolimus formulations with a 2 x 2 cross-over design. Intrasubject coefficients of variation calculated from analysis of variation in CYP3A5*1/*1+*1/*3 (n = 16) and CYP3A5*3/*3 (n = 13) groups were compared. The intrasubject CVs of AUClast and Cmax in the CYP3A5*3/*3 group were about 41.1% and 52.4% greater than those in the CYP3A5*1*1+*1/*3 group. The estimated total sample size for the bioequivalence study of tacrolimus with a 2 x 2 cross-over design was increased by 93.3% for AUClast (n = 30 versus 58) and 121.4% for Cmax (n = 28 versus 62) in the CYP3A5*3/*3 group compared with the CYP3A5*1/*1+*1/*3 group. The intraindividual variability of tacrolimus PK parameters may be associated with the CYP3A5 genotype. We propose that genotyping for CYP3A5 will provide a more efficient approach for bioequivalence designs and therapeutic drug monitoring.

Authors+Show Affiliations

Department of Pharmacology, Yonsei University College of Medicine, Seoul, South Korea.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

20010459

Citation

Yong Chung, Jae, et al. "CYP3A5*3 Genotype Associated With Intrasubject Pharmacokinetic Variation Toward Tacrolimus in Bioequivalence Study." Therapeutic Drug Monitoring, vol. 32, no. 1, 2010, pp. 67-72.
Yong Chung J, Jung Lee Y, Bok Jang S, et al. CYP3A5*3 genotype associated with intrasubject pharmacokinetic variation toward tacrolimus in bioequivalence study. Ther Drug Monit. 2010;32(1):67-72.
Yong Chung, J., Jung Lee, Y., Bok Jang, S., Ahyoung Lim, L., Soo Park, M., & Hwan Kim, K. (2010). CYP3A5*3 genotype associated with intrasubject pharmacokinetic variation toward tacrolimus in bioequivalence study. Therapeutic Drug Monitoring, 32(1), 67-72. https://doi.org/10.1097/FTD.0b013e3181c49a4c
Yong Chung J, et al. CYP3A5*3 Genotype Associated With Intrasubject Pharmacokinetic Variation Toward Tacrolimus in Bioequivalence Study. Ther Drug Monit. 2010;32(1):67-72. PubMed PMID: 20010459.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CYP3A5*3 genotype associated with intrasubject pharmacokinetic variation toward tacrolimus in bioequivalence study. AU - Yong Chung,Jae, AU - Jung Lee,Yoon, AU - Bok Jang,Seong, AU - Ahyoung Lim,Lay, AU - Soo Park,Min, AU - Hwan Kim,Kyung, PY - 2009/12/17/entrez PY - 2009/12/17/pubmed PY - 2010/4/3/medline SP - 67 EP - 72 JF - Therapeutic drug monitoring JO - Ther Drug Monit VL - 32 IS - 1 N2 - Tacrolimus is metabolized by CYP3A and has highly variable pharmacokinetics. To study the factors contributing to this high variability in pharmacokinetics and to investigate the possibility of genotype-specific clinical applications, the effect of differing CYP3A5 genotypes on the intrasubject coefficients of variation for tacrolimus was investigated. Genotyping for CYP3A5*3 was performed in healthy volunteers who had previously participated in the pharmacokinetic study of 2 tacrolimus formulations with a 2 x 2 cross-over design. Intrasubject coefficients of variation calculated from analysis of variation in CYP3A5*1/*1+*1/*3 (n = 16) and CYP3A5*3/*3 (n = 13) groups were compared. The intrasubject CVs of AUClast and Cmax in the CYP3A5*3/*3 group were about 41.1% and 52.4% greater than those in the CYP3A5*1*1+*1/*3 group. The estimated total sample size for the bioequivalence study of tacrolimus with a 2 x 2 cross-over design was increased by 93.3% for AUClast (n = 30 versus 58) and 121.4% for Cmax (n = 28 versus 62) in the CYP3A5*3/*3 group compared with the CYP3A5*1/*1+*1/*3 group. The intraindividual variability of tacrolimus PK parameters may be associated with the CYP3A5 genotype. We propose that genotyping for CYP3A5 will provide a more efficient approach for bioequivalence designs and therapeutic drug monitoring. SN - 1536-3694 UR - https://www.unboundmedicine.com/medline/citation/20010459/CYP3A5_3_genotype_associated_with_intrasubject_pharmacokinetic_variation_toward_tacrolimus_in_bioequivalence_study_ L2 - https://doi.org/10.1097/FTD.0b013e3181c49a4c DB - PRIME DP - Unbound Medicine ER -