The effect of malaria infection on the disposition of quinine and quinidine in the rat isolated perfused liver preparation.
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.
Mansor
S M
SM
Department of Pharmacology and Therapeutics, University of Liverpool, UK.
Ward
S A
SA
Edwards
G
G
Hoaksey
P E
PE
Breckenridge
A M
AM
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
D011803:Quinine; D011802:Quinidine