Effect of kolanut on the pharmacokinetics of the antimalarial drug halofantrine

Objective To study the effect of the concomitant consumption of kolanut, a caffeine-containing nut, on the pharmacokinetics of halofantrine. Methods A single dose of 500 mg halofantrine hydrochloride was orally administered either alone or concomitant with 12.5 g kolanut to 15 healthy male volunteers in a Latin-square randomized crossover design with a wash-out period of 6 weeks between treatments. Blood samples were collected and analyzed by HPLC for halofantrine and the active metabolite N-desbutylhalofantrine. Results Concomitant intake of kolanut with halofantrine significantly decreased C-max and AUC of both halofantrine and the metabolite desbutylhalofantrine, while no significant effect was observed for t (max) and t (1/2) of the compounds. In the case of halofantrine, C-max decreased from 119 to 98 +/- 32 ng/ml, and the AUC was reduced from 17,450 +/- 4,611 to 11,821 +/- 4,069 ng center dot h/ml. C-max of desbutylhalofantrine decreased from 124 +/- 41 to 62 +/- 23 ng/ml and the AUC from 13,341 +/- 4,749 to 7,359 +/- 3,018 ng center dot h/ml when kolanut was co-administered. Conclusions Co-administration of halofantrine and kolanut caused a significant decrease in the plasma concentrations of halofantrine and the active metabolite desbutylhalofantrine probably during adsorption of the drug due to complex formation. This indicates that caution should be exerted when the drug is taken together with caffeine-containing nutrients.