Efficacy and pharmacokinetics of a new intrarectal quinine formulation in children with Plasmodium falciparum malaria

1 Three groups of seven children aged 2-14 years with acute uncomplicated Plasmodium falciparum malaria received 12.8 mg kg(-1) quinine gluconate by the intrarectal route (new cream formulation) or 8 mg kg(-1) Quinimax(R) (a Cinchona alkaloid combination) by the intramuscular or intravenous (4 h infusion) route every 8 h for 3 days. Clinical and parasitological status was similar in the three groups at enrolment. 2 At 36 h, body temperature of all children of the three groups was returned to normal and remained so until day 7. 3 The decrease in parasitaemia did not differ between the three groups and the time required for a 50% fall in parasitaemia relative to baseline was 12.3 +/- 5.4, 18.2 +/- 6.1 and 14.5 +/- 4.2 h in the intrarectal, intramuscular and intravenous treatment groups, respectively. Parasitaemia expressed as a percentage of initial values was not significantly different in the three groups after 48 h of treatment (7.4 +/- 16.0, 4.1 +/- 4.2 and 2.2 +/- 3.8% in the intrarectal, intramuscular and intravenous treatment groups, respectively). All the patients were aparasitaemic by day 7. 4 The tolerability of the three treatments was good; in particular, no rectal irritation was reported with the cream formulation. 5 The t(max) occurred later after intrarectal (4.1 +/- 2.4 h) and intravenous infusion (3.8 +/- 0.5 h) than after intramuscular injection (1.6 +/- 1.3 h) (P=0.02). C-max was lower with the intrarectal (3.0 +/- 1.0 mg l(-1)) and intramuscular routes (3.2 +/- 0.7 mg l(-1)) than with the intravenous route (5.1 +/- 1.4 mg l(-1)) (P=0.003). Areas under the curve (AUC(0, 8 h)) were smaller with the intrarectal (17.0 +/- 7 mg l(-1) h) and intramuscular routes (19.4 +/- 4.8 mg l(-1) h) than with the intravenous route (27.8 +/- 8.2 mg l(-1) h) (P=0.02). The approximate bioavailability of intrarectal quinine from 0 to 8 h was 36% vs intravenous quinine and 51% vs intramuscular quinine. 6 The good tolerability and efficacy of this new intrarectal quinine formulation outweigh its low approximate bioavailability. This new approach might thus be a safe and effective alternative to intramuscular quinine injection for the treatment of children with acute uncomplicated Plasmodium falciparum malaria in the field.