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Title: Phenotyping CYP3A using midazolam in cancer and noncancer Asian patients
Authors: Lee, H.S.
Goh, B.C.
Fan, L.
Khoo, Y.M.
Wang, L. 
Lim, R.
Ong, A.B.
Chua, C.
Keywords: Cancer and noncancer Asian patients
Issue Date: 1-Mar-2003
Citation: Lee, H.S., Goh, B.C., Fan, L., Khoo, Y.M., Wang, L., Lim, R., Ong, A.B., Chua, C. (2003-03-01). Phenotyping CYP3A using midazolam in cancer and noncancer Asian patients. British Journal of Clinical Pharmacology 55 (3) : 270-277. ScholarBank@NUS Repository.
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 (Vss) 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.
Source Title: British Journal of Clinical Pharmacology
ISSN: 03065251
DOI: 10.1046/j.1365-2125.2003.01767.x
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