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- Title
Phenotyping CYP3A using midazolam in cancer and noncancer Asian patients.
- Authors
Lee, How Sung; Goh, Boon Cher; Fan, Lu; Khoo, Yok Moi; Wang, Lingzhi; Lim, Robert; Ong, Ai Bee; Chua, Charlotte
- Abstract
Aims To investigate CYP3A activity in cancer and noncancer Asian patients using midazolam and to reveal possible alternative traits for phenotyping CYP3A. Methods Intravenous midazolam 2.5 mg or 2.5–8 mg was administered to 27 cancer and 24 noncancer patients, respectively. Plasma was sampled at 0, 0.25, 0.5, 1, 1.5, 2, 3.5 and 5 h after intravenous ultrashort, 30 s infusion. Plasma midazolam and 1′-hydroxymidazolam concentrations were determined using GCMS. The disposition of midazolam and 1′-hydroxymidazolam in these patients was compared. Midazolam clearance was correlated with dose-normalized plasma midazolam concentrations (concentration/per dose). Results Clearance (CL) and steady state volume of distribution (V ss ) of midazolam (mean ± SD, 95% confidence level) in cancer (424 ± 155, 61.3 ml min-1 ; 1.21 ± 0.46, 0.18 l kg-1 ) and noncancer (407 ± 135, 57.1 ml min-1 ; 1.15 ± 0.33, 0.155 l kg-1 ) patients, respectively, were not different and comparable with published data. Clearance variability was 4–5 fold in both groups. Midazolam clearance correlated significantly with all plasma concentration/per dose at and after the 1-h time point, with a minimum correlation coefficient of r = 0.752, P < 0.001. Conclusions CYP3A activities determined with different doses of midazolam in cancer and noncancer Asian patients showed variability of 4–5-fold and were not different between groups. One to two-fold plasma midazolam concentrations per dose may be feasible as a simple alternative phenotypic trait for hepatic CYP3A activity determination.
- Subjects
ASIA; MIDAZOLAM; CANCER
- Publication
British Journal of Clinical Pharmacology, 2003, Vol 55, Issue 3, p270
- ISSN
0306-5251
- Publication type
Article
- DOI
10.1046/j.1365-2125.2003.01767.x