Intrarectal Quinimax ® (an association of Cinchona alkaloids) for the treatment of Plasmodium falciparum malaria in children in Niger: efficacy and pharmacokinetics

Abstract

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 ® (a quinine, quinidine, cinchonine, cinchonidine association) intrarectally. A further 11 children with malaria were treated with 12·5 mg/kg of the same Quinimax ® 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 (1·1 ± 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 ® 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.