Effect of chlorpheniramine on the pharmacokinetics of and response to chloroquine of Nigerian children with falciparum malaria

Chlorpheniramine (CP), a histamine Hi-receptor antagonist, enhances the eff icacy of chloroquine (CQ) in acute uncomplicated falciparum malaria. The ef fects of this combination therapy on the pharmacokinetic disposition of CQ is, however, unpredictable. A standard treatment with 25 mg CQ base per kg bodyweight was orally administered over 3 days, alone or in combination wit h CP, to 17 semi-immune Nigerian children with Plasmodium falciparum parasi taemia attending hospital in Lagos, Nigeria, and observed for 28 days. Whol e-blood CQ concentrations were monitored 14 times during the follow-up by h igh-performance liquid chromatography analysis of blood dried on filter pap er. Parasitaemia was determined on thick blood films stained with Giemsa, a nd treatment failures were established following the WHO classification for CQ resistance. Our pharmacokinetic data showed that the peak whole-blood C Q concentration was significantly increased (P < 0.05) by CP administration , and the time to achieve the peak was reduced in the presence of CP. The a rea under the first-moment drug-concentration-time curve was also significa ntly increased (P < 0.05) by CP administration. Treatment with CQ-CP combin ation resulted in a shorter parasite clearance time: (2.0 +/- 0.5 days) and a higher cure rate (87.5%) compared to treatment with CQ alone (3.5 +/- 0. 5 days; 66.7%). Our data suggest that CP enhanced the efficacy of CQ agains t resistant P. falciparum in acute uncomplicated malaria by increasing the uptake/concentration of CQ in resistant parasites.