Intrarectal pharmacokinetics of two formulations of quinine in children with falciparum malaria

Objective: To compare the intrarectal bioavailabilities of two parenteral formulations of quinine most available in French- (Cinchona alkaloid mixture) and English (hydrochloride salt) -speaking areas of Africa. Methods: The pharmacokinetics of quinine was investigated in four groups of 12 children with acute Plasmodium falciparum malaria receiving 8 mg/kg quinine base every 8 h either as hydrochloride salt or Cinchona alkaloid mixture by a slow 4-h intravenous infusion or intrarectal administration. Body temperature and parasitaemia were monitored, and blood quinine concentrations were measured by means of high-performance liquid chromatography. Results: At 72 h, all the children were aparasitaemic and apyretic. Quinine Cmax values were higher after intravenous infusion of the hydrochloride salt and Cinchona alkaloid mixture (6.9 ± 1.9 μg/ml and 5.2 ± 1.3 μg/ml) than after intrarectal administration (3.5 ± 1.4 μg/ml and 3.1 ± 1.6 μg/ ml), but tmax values were similar (3.6 ± 1.5, 4.2 ± 1.0, 4.0 ± 1.9, and 4.7 ± 2.0 h, respectively). Intrarectal relative bioavailabilities of hydrochloride salt solution (57%) and Cinchona alkaloid mixture (62%) were similar. Conclusion: Whatever the parenteral formulation of quinine, the blood concentration-time profiles of quinine were similar after intrarectal administration. Intrarectal administration of hydrochloride salt solution is a possible mode of quinine delivery in remote rural areas of Africa.