Binding of Quinine to Plasma Proteins in Falciparum Malaria

Abstract

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 less than 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.

Studies of mefloquine bioavailability and kinetics using a stable isotope technique: a comparison of Thai patients with falciparum malaria and healthy Caucasian volunteers.

“…Factors associated with acute infection such as impairment of the drug clearance mechanisms or reduced tissue binding may also be relevant. This suggestion is indirectly supported by observations on quinine pharmacokinetics in malaria where volume of distribution and clearance have been shown to be progressively reduced with increasing severity of infection, and plasma protein binding increases in severe disease (Silamut et al, 1985;White et al, 1982). However, in this study there was no significant difference between plasma protein binding of mefloquine in the malaria patients (98.4 ± 0.4%) and the healthy volunteers (98.2 ± 0.3%) (R. Brandt, personal communication).…”

Quinine induces reversible high‐tone hearing loss.

“…There is increased plasma protein binding of quinine in malaria (Silamut et al, 1985) principally because of increases in the acute phase protein, al-acid glycoprotein. In this study the mean concentration of free quinine was 6% of the total concentration.…”

“…Vital signs were measured four hourly and parasite counts were checked twice daily. Quinine was measured by high performance liquid chromatography with fluorescence detection and plasma protein binding was determined as described previously (Silamut et al, 1985).…”

Effect of Plasmodium falciparum malaria infection on the plasma concentration of alpha 1‐acid glycoprotein and the binding of quinine in Malawian children.

“…The free (unbound) concentration of quinine (QN) is likely to reflect the drug's efficacy and its toxicity. The free fraction fluctuates during malarial infection (Silamut et al, 1985), but the relationship between plasma concentrations of AGP and the free fraction of QN has not previously been described.…”