The Effect of Malaria Infection on the Disposition of Quinine and Quinidine in the Rat Isolated Perfused Liver Preparation

Abstract

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 < 0.001) and quinidine (AUC: 6642 ± 1304 vs 4808 ± 872 ng h mL−1, P < 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 < 0.001) and volume of distribution (Vd) (53.0 ± 13.3 vs 81.2 ± 23.7 mL g−1, P < 0.05) but no significant change in elimination half-life (t1/2) (1.93 ± 0.6 vs 1.37 ± 0.25 h, P > 0.05). With quinidine, however, MI resulted in decreased CL (0.38 ± 0.16 vs 0.64 ± 0.09, P < 0.05) with no change in Vd and a significant increase in t1/2 (1.62 ± 0.42 vs 0.88 ± 0.22, P < 0.01). In summary, the hepatic disposition of quinine and quinidine is altered in the malaria-infected rat.