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• W2052371389 abstract "The impact of P-glycoprotein (P-gp) on the distribution of quinine between brain and plasma was studied experimentally in mice. Administration of quinine (20 mg/kg, i.v.) to mdrla knockout mice resulted in enhanced brain concentrations of quinine as compared to the wild-type mice (7.9 ± 1.4 μg/g versus 1.6 ± 0.8 μg/g, respectively). Quinine concentrations and quinine-to-3-hydroxyquinine ratio in plasma were similar in normal and P-gp-deficient mice. The effect of intravenously administered drugs before quinine (20 mg/kg, i.v.) was evaluated on brain uptake and biotransformation of quinine in mice. Cyclosporine A (50 mg/kg), erythromycine (40 mg/kg), verapamil (5 mg/kg) or mefloquine (20 mg/kg) increased the brain-to-plasma quinine concentration ratio (by factors of 3.8-, 1.8-, 1.9- and 2.5-fold, respectively) and the quinine-to-3-hydroxyquinine ratio in plasma (by factors 2.1-, 3.7-, 1.8- and 2.0-fold, respectively). After cinchonine (40 mg/kg) and halofantrine (40 mg/kg) pre-treatment, the brain-to-plasma ratio for quinine increased by factor of 2.3 and 1.8, respectively without changes of quinine or metabolite concentrations in plasma. Doxycycline (20 mg/kg), artesunate (50 mg/kg) or artemether (50 mg/kg) did not alter quinine disposition. These results confirm in vivo that quinine is a substrate for mdr1a P-gp. Drug associations led not only to metabolic interactions but also increased quinine uptake by tissues protected by P-gp. Such interactions may have implications for the improvement of chemotherapy but should be also taken into account for potential enhancement of adverse effects." @default.
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• W2052371389 date "2007-10-01" @default.
• W2052371389 modified "2023-10-06" @default.
• W2052371389 title "Increased uptake of quinine into the brain by inhibition of P-glycoprotein" @default.
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• W2052371389 doi "https://doi.org/10.1016/j.ejps.2007.06.007" @default.
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