Rifabutin reduces systemic exposure of an antimalarial drug 97/78 upon co-administration in rats: An in-vivo &in-vitro analysis

Asian Pacific Journal of Tropical Medicine
Yeshwant SinghShio K Singh

Abstract

To determine the potential drug-drug interactions between anti-malarial candidate 97/78 and anti-tubercular drug rifabutin in-vivo in rats followed by in-vitro investigation of the underlying mechanisms of drug interaction. Single oral dose study was conducted in male and female rats at 40 mg/kg and 70 mg/kg for 97/78 and rifabutin respectively. It was reported that rifabutin co-administration altered pharmacokinetics of 97/63 (active metabolite of 97/78). A significant decrease was reported in the systemic exposure of 97/63 by a factor of 3-4. The AUC0-last values were (4.03 ± 0.60) and (5.44 ± 1.15) μg h mL(-1) upon 97/78 administration alone, while the values were decreased to (1.13 ± 0.10) and (1.23 ± 1.13) μg h mL(-1) upon rifabutin co-administration in male and female rats respectively. Statistically significant differences were also reported in Cmax and Tmax values upon rifabutin co-administration. In-vitro drug metabolism study in rat liver microsomes has shown that the metabolism of 97/63 was increased by 10%-12% upon rifabutin co-incubation. The extent of plasma protein binding of 97/63 was found to be decreased from 54%-55% to 6%-8% upon rifabutin addition. It was concluded that rifabutin co-administration altered PK...Continue Reading

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