Effect of kolanut on the pharmacokinetics of the antimalarial drug halofantrine

Abstract

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 179 ± 119 to 98 ± 32 ng/ml, and the AUC was reduced from 17,450 ± 4,611 to 11,821 ± 4,069 ng·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·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.