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

Analysis of the antimalarial drug halofantrine and its major metabolite N-desbutylhalofantrine in human plasma by high performance liquid chromatography.

The determination of halofantrine and its major metabolite N-desbutylhalofantrine in human plasma by reversed phase high-pressure liquid chromatography is described. The method involves protein precipitation of plasma samples by acetonitrile followed by basification with sodium hydroxide and subsequent liquid-liquid extraction using hexane-diethyl ether (1:1, v/v). The chromatographic separation was carried out on a C-18 column with a mobile phase consisting of methanol/0.05 M KH2PO4 (78:22, v/v) containing 55 mM perchloric acid. Chlorprothixen was used as internal standard. The relative standard deviations of intraday and interday precision for both compounds were less than 7%, the relative standard deviation of the accuracy did not exceed 7.1% at concentrations of 50 and 300 ng/ml. This method is simple, rapid, sensitive and cost effective and was applied to the determination of the pharmacokinetics of halofantrine and N-desbutylhalofantrine in two healthy male volunteers after an oral administration of 500 mg halofantrine. Moreover, the influence of the frequently consumed kolanut on the pharmacokinetics of halofantrine was investigated.

Kinetics of thermal decomposition of 4-carboxyl-2,6-dinitrobenzenediazonium ion (CDNBD).

The kinetics of thermal decomposition of 4-carboxyl-2,6-dinitrobenzenediazonium ion (CDNBD), an arenediazonium ion newly developed as a derivatizing reagent for drug analysis, are described. The arenediazonium ion, in an optimized concentrated sulfuric acid/orthophosphoric acid medium, was incubated for various time intervals at 30 degrees, 45 degrees, 55 degrees , 65 degrees , 75 degrees, and 85 degrees C. The amount of ion left after each time interval was quantified selectively by colorimetric assay at 490 nm, using mefenamic acid as a model diazo-coupling component. The rate constants for the decomposition were determined graphically. An Arrhenius plot was used to delineate the dependence of the rate constant on temperature and to predict the half-life at 25 degrees C and lower temperatures. The diazonium ion decomposed by first-order kinetics. The rate constants of decomposition, which increased progressively with temperature, were 3.18 +/- 0.41 x 10(-5), 1.19 +/- 0.07 x 10(-4), 4.87 +/- 0.15 x 10(-4), 12.88 +/- 0.73 x 10(-4), and 21.32 +/- 2.74 x 10(-4) (s(-1)) with corresponding half-lives of 363, 97.06, 23.72, 8.97, and 5.42 min at 30 degrees, 45 degrees, 55 degrees, 65 degrees, and 75 degrees C, respectively. CDNBD is highly stable in concentrated acid medium, with half-life values of about 10 h, 10 days, and 7.3 months at 25 degrees, 0 degrees, and -20 degrees C, respectively. The reagent stability profile shows that it could be readily adapted for routine applications in instrumental chemical analysis.