Shin, K-H Choi, M. H. Lim, K. S. Yu, K-S Jang, I-J Cho, J-Y 2024-01-20T11:03:48Z 2024-01-20T11:03:48Z 2021-09-05 2013-11 0009-9236 https://pubs.kist.re.kr/handle/201004/127470 This study aimed to evaluate endogenous metabolic markers of hepatic cytochrome P450 (CYP)3A activity in healthy subjects using a metabolomics approach. Twenty-four subjects received the following medication during the following three study periods: 1 mg of i.v. midazolam alone (control phase), 1 mg of i.v. midazolam after 4 days of pretreatment with 400 mg of ketoconazole once daily (CYP3A-inhibited phase), and 2.5 mg of i.v. midazolam after 10 days of pretreatment with 600 mg of rifampicin once daily (CYP3A-induced phase). During each study period, 24 h before and after the administration of midazolam, urine samples were collected at 12-h intervals for metabolomic analyses. We derived an equation to predict midazolam clearance (CL) based on several of these markers. We demonstrated that a combination of the concentrations and ratios of several endogenous metabolites and the CYP3A5*3 genotype is a reliable predictive marker of hepatic CYP3A activity as assessed by i.v. administration of midazolam. English WILEY CYTOCHROME-P450 3A4 IN-VIVO 4-BETA-HYDROXYCHOLESTEROL HUMANS INDUCTION INHIBITION 6-BETA-HYDROXYCORTISOL PHARMACOKINETICS IDENTIFICATION EXPRESSION Evaluation of Endogenous Metabolic Markers of Hepatic CYP3A Activity Using Metabolic Profiling and Midazolam Clearance Article 10.1038/clpt.2013.128 1 CLINICAL PHARMACOLOGY & THERAPEUTICS, v.94, no.5, pp.601 - 609 CLINICAL PHARMACOLOGY & THERAPEUTICS 94 5 601 609 scie scopus 000326090100023 2-s2.0-84886722102 Pharmacology & Pharmacy Pharmacology & Pharmacy Article CYTOCHROME-P450 3A4 IN-VIVO 4-BETA-HYDROXYCHOLESTEROL HUMANS INDUCTION INHIBITION 6-BETA-HYDROXYCORTISOL PHARMACOKINETICS IDENTIFICATION EXPRESSION metabolomics steroid midazolam rifampicin drug evaluation cytochrome P450