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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 |
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