title: The effect of malaria infection on the disposition of quinine and quinidine in the rat isolated perfused liver preparation.
abstract: The effect of malaria on the disposition of quinine and quinidine was studied in livers isolated from young rats infected with merozoites of Plasmodium berghei, a rodent malaria model, and non-infected controls. Following bolus administration of quinine (1 mg) or quinidine (1 mg) to the 100 mL recycling perfusion circuit, perfusate was sampled (0-4 h) and plasma assayed for quinine and quinidine by HPLC. Higher quinine (AUC:6470 +/- 1101 vs 3822 +/- 347 ng h mL-1, P less than 0.001) and quinidine (AUC: 6642 +/- 1304 vs 4808 +/- 872 ng h mL-1, P less than 0.05) concentrations were observed during malaria infection (MI). MI resulted in decreased quinine clearance (CL) (0.33 +/- 0.08 vs 0.64 +/- 0.09 mL min-1 g-1, P less than 0.001) and volume of distribution (Vd) (53.0 +/- 13.3 vs 81.2 +/- 23.7 mL g-1, P less than 0.05) but no significant change in elimination half-life (t1/2) (1.93 +/- 0.6 vs 1.37 +/- 0.25 h, P greater than 0.05). With quinidine, however, MI resulted in decreased CL (0.38 +/- 0.16 vs 0.64 +/- 0.09, P less than 0.05) with no change in Vd and a significant increase in t1/2 (1.62 +/- 0.42 vs 0.88 +/- 0.22, P less than 0.01). In summary, the hepatic disposition of quinine and quinidine is altered in the malaria-infected rat.
authors.affiliation: Department of Pharmacology and Therapeutics, University of Liverpool, UK.
authors.forename: S M
authors.initials: SM
authors.lastname: Mansor
authors.forename: S A
authors.initials: SA
authors.lastname: Ward
authors.forename: G
authors.initials: G
authors.lastname: Edwards
authors.forename: P E
authors.initials: PE
authors.lastname: Hoaksey
authors.forename: A M
authors.initials: AM
authors.lastname: Breckenridge
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008288:Malaria / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D010962:Plasmodium berghei; D011802:Quinidine / Q000493:pharmacokinetics*; D011803:Quinine / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D013056:Spectrophotometry, Ultraviolet
chemical_list: D011803:Quinine; D011802:Quinidine