Severe global malnutrition and cerebral malaria have a similar effect on quinine pharmacokinetics in children. Moderate malnutrition does not potentiate cerebral malaria-mediated modifications of quinine disposition. These results suggest that current parenteral quinine regimens can be used, unmodified, to treat children with both malaria and malnutrition.

1Three 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 (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. 2At 36 h, body temperature of all children of the three groups was returned to normal and remained so until day 7. 3The 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. 4The tolerability of the three treatments was good; in particular, no rectal irritation was reported with the cream formulation. 5The tmax 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). Cmax 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. 6The 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.

No abstract