RT Journal Article SR Electronic T1 Pharmacokinetics of Midazolam and 1′-Hydroxymidazolam in Chinese with Different CYP3A5 Genotypes JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 1491 OP 1496 DO 10.1124/dmd.30.12.1491 VO 30 IS 12 A1 Shih, Pei-Shan A1 Huang, Jin-Ding YR 2002 UL http://dmd.aspetjournals.org/content/30/12/1491.abstract AB The CYP3A subfamily represents the most abundant cytochrome P450 in the human liver and gastrointestinal tract and plays very important role in xenobiotic metabolism. CYP3A5 is expressed in a relatively small population of whites and Orientals. We recruited 42 Chinese volunteers to determine the genotypes of CYP3A5 by polymerase chain reaction-restriction fragment length polymorphism. Genotype analyses revealed thatCYP3A5*3 allele existed in 39 of 42 volunteers.CYP3A5*4 and CYP3A5*5 alleles were found in one volunteer each; and CYP3A5*2 andCYP3A5*6 alleles were not found. The most frequentCYP3A5*3 allele is known not to express CYP3A5. We excluded other genotypes of CYP3A5 to study the significance of CYP3A5*3 in midazolam pharmacokinetics. In this study, each volunteer was given a midazolam tablet (7.5 mg) orally. Blood samples were collected to analyze the time-dependent concentrations of midazolam and 1′-hydroxymidazolam by high-performance liquid chromatography. The average area under plasma concentration curve (AUC, 0–8 h) of midazolam was 9237 ± 1050 ng-min/ml (mean ± S.E.M.) in homozygous CYP3A5*3(n = 14) subjects and 7934 ± 768 ng-min/ml in heterozygous CYP3A5*1/*3 (n = 12) subjects, respectively. The average AUC (0–8 h) of 1′-hydroxymidazolam was 3748 ± 427 ng-min/ml in homozygous CYP3A5*3subjects and 3920 ± 402 ng-min/ml in heterozygousCYP3A5*1/*3 subjects. The results indicated that the pharmacokinetics of midazolam and 1′-hydroxymidazolam was independent of CYP3A5 expression. Although the genetic polymorphism of CYP3A5 is well known, the results of this study suggested that the clinical consequence might be insignificant. The American Society for Pharmacology and Experimental Therapeutics