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| Pharmacokinetics of midazolam and 1 '-hydroxymidazolam in Chinese with different CYP3A5 genotypes |
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| Author(s): Shih PS, Huang JD |
| Source: DRUG METABOLISM AND DISPOSITION Volume: 30 Issue: 12 Pages: 1491-1496 Published: DEC 2002 |
| Times Cited: 78 References: 29 |
| Abstract: 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 that CYP3A5*3 allele existed in 39 of 42 volunteers. CYP3A5*4 and CYP3A5*5 alleles were found in one volunteer each; and CYP3A5*2 and CYP3A5*6 alleles were not found. The most frequent CYP3A5*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*3 subjects and 3920 +/- 402 ng-min/ml in heterozygous CYP3A5*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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Huang, JD (reprint author), Natl Cheng Kung Univ, Coll Med, Dept Pharmacol, 1 Univ Rd, Tainan 70101, Taiwan |
Addresses:
1. Natl Cheng Kung Univ, Coll Med, Dept Pharmacol, Tainan 70101, Taiwan |
| Publisher: AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA |
| Subject Category: Pharmacology & Pharmacy |
| IDS Number: 615KK |
| ISSN: 0090-9556 |
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