Research in Experimental Antimalarial Chemotherapy.

The primary objectives of the project on Research on Antimalarial Chemotherapy Novel approach to combination therapy in multidrug resistant malaria focused on confirmation of reversal of chloroquine resistance in isolates of P. falciparum from Nigeria and molecular biology, pharmacokinetics and biochemistry of the reversal phenomenon. The major objectives of the project were accomplished. Efforts during the project resulted in modification of standard in vitro techniques for continuous cultivation of P. falciparum in Nigeria. The modified technique is now in routine use at the cooperative malaria laboratory in the department of Pharmacology and Therapeutics University of Ibadan, Nigeria. Reversal of mefloquine resistance with penfluridol and reversal of chloroquine resistance with promethazine WRBL 50601, chlorpheniramine, diphenhydramine and pyrilamine were identified and published in 1991 and 1992. The findings on reversal of chloroquine resistance with promethazine and chlorpheniramine represent the first demonstration of the reversal phenomenon with drugs prescribed as adjunct in chemotherapy of malaria in an endemic area. Subsequent efforts were allocated to studies on pharmacokinetics and clinical efficacy of potential combinations of chlorpheniramine with antimalarial drugs in human volunteers and animal models. Other studies accomplished during the period include clinical efficacy of artemether, mefloquine and suphadoxine-pyrimethamine. Nine manuscripts have been published, two are being prepared for publication.