INTRARECTAL QUINIMAX(R) (AN ASSOCIATION OF CINCHONA ALKALOIDS) FOR THE TREATMENT OF PLASMODIUM-FALCIPARUM MALARIA IN CHILDREN IN NIGER - EFFICACY AND PHARMACOKINETICS

In an attempt to avoid the complications associated with intramuscular quinine administration, we assessed the intrarectal route. Sixty-six children aged from 2 to 10 years with Plasmodium falciparum malaria were included in the study, which took place in Niamey, Niger. Fifty-five children were given 20 mg/kg of the diluted injectable form of Quinimax(R) (a quinine, quinidine, cinchonine, cinchonidine association) intrarectally. A further 11 children with malaria were treated with 12.5 mg/kg of the same Quinimax(R) solution by the intramuscular route. All the children were treated twice a day for 3 d. Blood samples were drawn from 20 children (15 treated intrarectally and 5 intramuscularly) for a kinetic study. Both modes of administration were well tolerated. Mean fever clearance times ( +/- standard errors) were 48.6 +/- 2.7 h and 35.9 +/- 2.2 h in the intrarectal and intramuscular groups, respectively (P = 0.05). Mean parasite clearance times ( +/- standard errors) and mean times to achieve 50% reduction in parasitaemia ( +/- standard errors) were similar after intrarectal (46.5 +/- 5.7 h and 7.8 +/- 0.9 h respectively) and intramuscular administration (27.4 +/- 3.6 h and 8.7 +/- 1.7 h, respectively). T-max. after intrarectal administration (2.7 +/- 0.4 h) did not differ significantly from the value after intramuscular administration (11 +/- 0.6 h), but C-max. and the area under the concentration-time curve from 0 to 48 h were lower (4.9 +/- 0.6 mg/L and 230.0 +/- 9.6 mg/L.h, respectively) than after intramuscular administration (9.1 +/- 1.2 mg/L and 356.0 +/- 4.2 mg/L.h, respectively) (P < 0.001). Compared to the intramuscular route, intrarectal Quinimax(R) bioavailability was 40%. The tolerability and efficacy of this alkaloids association administered by the intrarectal route were satisfactory, while bioavailability should be improved by the use of a formulation specifically adapted to this route.