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Influence of the CYP3A5 and MDR1 genetic polymorphisms on the pharmacokinetics of tacrolimus in healthy Korean subjects

Authors
 Ji H. Choi  ;  Yoon J. Lee  ;  Kyungsoo Park  ;  Kyung H. Kim  ;  Jong-Eun Lee  ;  Seong B. Jang 
Citation
 British Journal of Clinical Pharmacology, Vol.64(2) : 185-191, 2007 
Journal Title
 British Journal of Clinical Pharmacology 
ISSN
 0306-5251 
Issue Date
2007
Abstract
AIMS: To determine the frequencies of the genotypes of CYP3A5 and MDR1 and to examine the influence of the polymorphisms of these genes on tacrolimus pharmacokinetics in the Korean population. METHODS: Twenty-nine healthy Koreans who participated in the previous tacrolimus pharmacokinetic study were genotyped for CYP3A4*1B, CYP3A5*3, MDR1 c.1236C-->T, MDR1 c.2677G-->A/T and MDR1 c.3435C-->T. The relationship between the genotypes so obtained and tacrolimus pharmacokinetics observed in the previous study was examined. RESULTS: No subject in this study had the CYP3A4*1B variant. The observed frequencies of CYP3A5*1/*1, *1/*3, and *3/*3 were 0.069 [confidence interval (CI) -0.023, 0.161], 0.483 (CI 0.301, 0.665) and 0.448 (CI 0.267, 0.629), respectively. AUC(0-infinity) for the CYP3A5*1/*1 or *1/*3 genotype was 131.5 +/- 44.8 ng h ml(-1) (CI 109.6, 153.5), which was much lower compared with the CYP3A5*3/*3 genotype of 323.8 +/- 129.3 ng h ml(-1) (CI 253.5, 394.1) (P = 2.063E-07). Similarly, C(max) for the CYP3A5*1/*1 or *1/*3 genotype was 11.8 +/- 3.4 ng ml(-1) (CI 10.1, 13.5), which was also much lower compared with the CYP3A5*3/*3 genotype of 24.4 +/- 12.3 ng ml(-1) (CI 17.8, 31.1) (P = 0.0001). However, there was no significant difference in tacrolimus pharmacokinetics among the MDR1 diplotypes of CGC-CGC, CGC-TTT, CGC-TGC, TTT-TGC or TTT-TTT (P = 0.2486). CONCLUSIONS: This study shows that the CYP3A5*3 genetic polymorphisms may be associated with the individual difference in tacrolimus pharmacokinetics. An individualized dosage regimen design incorporating such genetic information would help increase clinical efficacy of the drug while reducing adverse drug reactions.
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T200700723.pdf Download
DOI
10.1111/j.1365-2125.2007.02874.x
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
김경환(Kim, Kyung Hwan)
박경수(Park, Kyungsoo) ORCID logo https://orcid.org/0000-0002-6972-1143
장성복(Jang, Seong Bok)
최지하(Choi, Ji Ha)
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/95750
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