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खुला एक्सेस

अमूर्त

Possible Interethnic Differences in Rifampin Pharmacokinetics:Comparison of Middle Eastern Arabs with other Populations

Hisham S Abou-Auda

Objectives: The pharmacokinetics of rifampin and its major metabolite desacetylrifampin after oral administration of rifampincapsules were studied in 24 healthy Middle Eastern Arab male volunteers. Middle Eastern Arabs were compared with Mexicans, Italians, Indians, Estonians, British and American Caucasians with respect to pharmacokinetic parameters of rifampin to seek evidence for polymorphism in rifampin pharmacokinetics. Methods: Each subject received a single dose of 600 mg (2×300 mg capsules) of rifampin after an overnight fast and plasma samples were drawn at specified times for a period up to 16 h after drug administration. Concentration of rifampin and its metabolie were determined using an accurate HPLC method. The data for other ethnic groups were extracted from published studies or solicited from investigators. Results: The maximum rifampin plasma concentration (Cmax) was 8.86 ± 2.74 μg/ml (Mean ± SD) and the time to reach maximum plasma concentration (Tmax) was 1.88 ± 1.12h.The maximum desacetylrifampin plasma concentration (Cmax,Met) averaged 0.96 ± 0.32 g/ml (Mean ± SD) and the time to peak plasma concentration of the metabolite (Tmax,Met) averaged 4.29 ± 1.3h.No statistically significant differences in most of rifampin pharmacokinetic parameters between Middle Eastern Arabs and other ethnic groups. Probit transformation of AUC data revealed a bimodal probit plot with breakpoint corresponding to an AUC of about 60 μg.h/ml. Conclusions: The data support the possibility of existence of interethnic differences in rifampin pharmacokinetics. American Caucasians, Tunisians and Middle Eastern Arabs could be grouped in one category, whereas Italians, Indians and Mexicans could be grouped in another category with respect to rifampin pharmacokinetics.