Pharmacokinetics of Quinimax (R) suppositories in children with malaria - A preliminary study

Objective: The disposition of Quinimax(R) (a Cinchona alkaloid combination of quinine, quinidine, cinchonine and cinchonidine), administered as a supp ository, was evaluated in children with uncomplicated malaria. Methods: The pharmacokinetics of a single initial dose of Quinimax(R), admi nistered as a suppository (20 mg/kg), were compared with those of either an intramuscular injection (8 mg/kg) in a lateral thigh muscle or a slow 4-ho ur intravenous injection (8 mg/kg) in 15 children with uncomplicated malari a. After the initial dose, all children received an 8 mg/kg oral dose every 8 hours for 3 days. Results: The peak plasma concentration (C-max) and area under the plasma co ncentration-time curve from 0 to 8 hours (AUC(0-8h)) were similar after the three routes of administration. The time to C-max(t(max)) value was shorte r after intrarectal (1.7 +/- 0.4h) and intramuscular (1.9 +/- 0.7h) than af ter intravenous (3.8 +/- 0.2h) administration. The absolute bioavailability of intrarectal quinine from 0 to 8 hours was 43%. The treatments were well tolerated and the children were apyretic and aparasitaemic within the 7 da ys. Conclusions: These data confirm that administration via the intrarectal rou te is a possible mode of quinine delivery, but a mon appropriate galenic fo rmulation than Quinimax(R) suppositories needs to be evaluated for the earl y treatment of childhood malaria in remote rural areas of Africa.