alexa Pharmacokinetics of tolbutamide in ethnic Chinese.
Pharmaceutical Sciences

Pharmaceutical Sciences

Pharmaceutica Analytica Acta

Author(s): Gross AS, Bridge S, Shenfield GM

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Abstract AIMS: Ethnic differences in drug disposition have been described for many drugs. Despite the widespread use of tolbutamide in Asian populations, the pharmacokinetics of tolbutamide, a CYP2C9 substrate, have not been described in ethnic Chinese. METHODS: The pharmacokinetics of tolbutamide (500 mg orally) were studied in 10 young, healthy volunteers (seven male/three female; age 21-29 years), each of whom had four ethnic Chinese grandparents. Plasma concentrations of tolbutamide were measured for 32 h post-dose by high performance liquid chromatography. The concentrations of hydroxytolbutamide and carboxytolbutamide were also measured in urine for 32 h post-dose. Noncompartmental pharmacokinetic parameters were calculated using standard equations and compared with those previously reported in Caucasian subjects using the Mann-Whitney U test. RESULTS: Pharmacokinetic parameters in Chinese (mean+/-s.d.) including Cmax (63+/-11 microg ml(-1)), tmax (median 3.3 h; range 1.6-6.0 h), V/F (9.1+/-1.7 l) and t1/2, (9.1 h; harmonic mean) were similar to the values in Caucasians. CL/F (637+/-88 ml h(-1)) was higher in Chinese than Caucasians. The urinary recoveries of hydroxytolbutamide (13+/-1\% of dose) and carboxytolbutamide (68+/-5\% of dose) and the partial apparent metabolic clearance (0.15+/-0.02 ml min(-1) kg(-1)) in Chinese were comparable with Caucasians. CONCLUSIONS: The pharmacokinetics of tolbutamide have been described in ethnic Chinese and the disposition is similar to that reported in Caucasians. This study suggests that there is no substantial ethnic difference in the tolbutamide hydroxylase activity of CYP2C9.
This article was published in Br J Clin Pharmacol and referenced in Pharmaceutica Analytica Acta

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