Quinine impairs quinidine clearance in rat perfused liver

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Abstract
We have examined the disposition of the cinchona alkaloids quinine and quinidine in the rat recirculating isolated perfused liver preparation. When administered as separate 1 mg doses, the hepatic clearances of quinine and quinidine were similar to the hepatic perfusate rate of 10 mL min−1. When 1 mg of each was administered simultaneously, mean hepatic clearance of quinine was unchanged (9·00 ± 2·20 mL min−1 separate dosage, n = 7; 6·87 ± 1·77 mL min−1 simultaneous dosage, n = 7; P > 0·05). By contrast, mean hepatic clearance of quinidine was reduced significantly by concomitant quinine (10·6 ± 1·72 mL min−1 separate dosage, n = 7; 4·82 ± 1·25 mL min−1 simultaneous dosage, n = 7; P < 0·05). There was no significant difference in volumes of distribution when each alkaloid was administered separately (131 ± 46 mL quinine, 129 ± 21 mL quinidine; P > 0·05) but concomitant quinine administration increased quinidine volume of distribution to 169 ± 30 mL (P < 0·05). Four further experiments with simultaneous dosages of 0·5 mg of each alkaloid produced similar findings, indicating that the interactions did not derive from nonlinear drug disposition.

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