ArticleBritish journal of clinical pharmacology2003
Phenotyping CYP3A using midazolam in cancer and noncancer Asian patients.
Article in British journal of clinical pharmacology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed, 6 citations in OpenAlex.
- CYP3A Activity in End-of-Life Cancer Patients Measured by 4β-Hydroxycholesterol/cholesterol Ratio, in Men and Women.Cancers · 2021Article
- Population pharmacokinetic modelling to assess the impact of CYP2D6 and CYP3A metabolic phenotypes on the pharmacokinetics of tamoxifen and endoxifen.British journal of clinical pharmacology · 2014Article
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8 authors at 2 institutions in 1 country.
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Abstract
aimsTo investigate CYP3A activity in cancer and noncancer Asian patients using midazolam and to reveal possible alternative traits for phenotyping CYP3A.
methodsIntravenous 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).
resultsClearance (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.
conclusionsCYP3A 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.
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