Comparative cardiac effects of antimalarial drug halofantrine with or without concomitant administration of kolanut or fluconazole in healthy volunteers

Abstract

Background: There is rekindled interest in the cardiotoxicity of antimalarial medicines. Halofantrine is associated with QT interval prolongation. Fluconazole and kolanut alter the pharmacokinetics of halofantrine. Objectives: The study assessed the electrocardiographic changes of concomitant administration of kolanut or fluconazole with halofantrine and the effects on the QTc interval. Methods: Eighteen healthy volunteers received a single oral dose of halofantrine, halofantrine with kolanut or halofantrine with fluconazole in a crossover study. Twelve lead electrocardiography (ECG) was performed to measure the PR and QT interval (QTc). Statistical analysis was with SPSS at 5% level of significance. Results: PR intervals were shortened by halofantrine alone and halofantrine with kolanut (169.29 28.67 to 165.29 28.007 and 172.73 29.843 to 163.00 18.336ms) but was prolonged by halofantrine with fluconazole (177.70 27.394 to 186.59 44.434ms). There was prolongation of QTc (384.76 21.727 to 394.12 21.525; 381.36 22.29 to 388.30 17.26 and 382.35 20.08 to 390.84 21.97) in all the three treatment groups at 6 hours, p>0.05. One subject on halofantrine and fluconazole had QTc >440ms. Pre-treatment PR interval (PR0) correlated well with post-treatment PR6, and with PR14 r= 0.519, p= 0.014; r=0.664, p=0.013. Conclusion: Concomitant intake of kolanut with halofantrine was significantly decrease cardiac effect of halofantrine. Keywords: Drug interaction; fluconazole; halofantrine; kolanut; malaria; QT prolongation.