Binding of Quinine to Plasma Proteins in Falciparum Malaria

Kamolrat SilamutHospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Tropical Medicine Unit, Nuffield Department of Clinical Medicine, University of Oxford, England and Department of Tropical Medicine, Liverpool School of Tropical Medicine, 420/6 Rajvithi Road, Bangkok 10400, Thailand

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Nicholas J. WhiteHospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Tropical Medicine Unit, Nuffield Department of Clinical Medicine, University of Oxford, England and Department of Tropical Medicine, Liverpool School of Tropical Medicine, 420/6 Rajvithi Road, Bangkok 10400, Thailand

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Sornchai LooareesuwanHospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Tropical Medicine Unit, Nuffield Department of Clinical Medicine, University of Oxford, England and Department of Tropical Medicine, Liverpool School of Tropical Medicine, 420/6 Rajvithi Road, Bangkok 10400, Thailand

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David A. WarrellHospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Tropical Medicine Unit, Nuffield Department of Clinical Medicine, University of Oxford, England and Department of Tropical Medicine, Liverpool School of Tropical Medicine, 420/6 Rajvithi Road, Bangkok 10400, Thailand

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Plasma protein binding of quinine was measured in 12 patients with cerebral malaria on the first and seventh day of treatment, and in 7 patients with uncomplicated falciparum malaria on admission and also one month later. Binding was significantly higher and therefore the proportion of free drug was lower in cerebral malaria patients (free:total quinine concentration; 7.2 ± 3.5%, mean ± SD, on admission; 7.4 ± 5.3% on day 7) compared with uncomplicated malaria patients on admission (10.2 ± 5.8%) or following recovery (11.0 ± 5.5%, n = 6) P = 0.011. Binding was significantly correlated with the red cell/total concentration ratio r = 0.56, P < 0.0001. The ratio of cerebrospinal fluid to free (unbound) plasma quinine was 0.55 ± 0.33 which suggests that quinine does not freely cross the blood brain barrier. These findings are relevant to the interpretation of total plasma or serum concentration, and may explain the rarity of serious quinine toxicity in severe falciparum malaria.

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