CYP3A5*3 genotype associated with intrasubject pharmacokinetic variation toward tacrolimus in bioequivalence study

Jae Yong Chung, Yoon Jung Lee, Seong Bok Jang, Lay Ahyoung Lim, Min Soo Park, Kyung Hwan Kim

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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 × 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 AUC last and C max 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 × 2 cross-over design was increased by 93.3% for AUC last (n = 30 versus 58) and 121.4% for C max (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.

Original languageEnglish
Pages (from-to)67-72
Number of pages6
JournalTherapeutic Drug Monitoring
Issue number1
Publication statusPublished - 2010 Feb 1


All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

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