title: Quinine impairs quinidine clearance in rat perfused liver.
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.
authors.affiliation: Department of Medicine, University of Melbourne, Repatriation Hospital, Victoria, Australia.
authors.forename: G W
authors.initials: GW
authors.lastname: Mihaly
authors.forename: H
authors.initials: H
authors.lastname: Scott
authors.forename: M K
authors.initials: MK
authors.lastname: Hyman
authors.forename: D J
authors.initials: DJ
authors.lastname: Morgan
authors.forename: R A
authors.initials: RA
authors.lastname: Smallwood
mesh_terms: D000818:Animals; D003864:Depression, Chemical; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011802:Quinidine / Q000493:pharmacokinetics*; D011803:Quinine / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
chemical_list: D011803:Quinine; D011802:Quinidine