Dose-dependent resorption of quinine after intrarectal administration to children with moderate Plasmodium falciparum malaria

Abstract

The pharmacokinetics of increasing doses of an intrarectal Cinchona alkaloid combination containing 96.1% quinine, 2.5% quinidine, 0.68% cinchonine, and 0.67% cinchonidine (Quinimax) was compared to that of parenteral regimens in 60 children with moderate malaria. Quinine exhibited a nonlinear pharmacokinetics, suggesting a saturation of rectal resorption. When early rejections appeared, blood quinine concentrations decreased by 30 to 50% and were restored by an immediate half-dose administration of the drug. Rectal administration of doses of 16 or 20 mg/kg of body weight led to concentration-time profiles in blood similar to those of parenteral regimens and could be an early treatment of childhood malaria.

FIG. 1.

Profiles for children with P. falciparum malaria of concentrations of quinine in blood versus time after the following treatments: IV8 (•), IM12 (▪), IR8 (□), IR12 (○), IR16 (▵), and IR20 (▿) (data are median values).

FIG. 2.

Profiles for children with P. falciparum malaria of concentrations of quinine in blood versus time after IR20 treatment without (▪) and with (•) early rejections. Early rejections were immediately followed by the administration of a half-dose (▴) of 10 mg/kg (data are median values).