PHARMACOKINETICS OF LUMEFANTRINE IN HEALTHY PAKISTANI VOLUNTEERS

Abstract

Objective: To study the pharmacokinetics of lumefantrine in healthy Pakistani volunteers so as to see the adequacy of the regimen in vogue for the treatment of malaria and prevention of recrudescence.
Place and duration of study: Department of Pharmacology and Therapeutics, Army Medical College Rawalpindi, from December 2006 to December 2007.
Study design: Quasi experimental study.
Subjects and Methods: Twelve healthy Pakistani male adult volunteers after informed consent participated in the study. Plasma concentration time profiles were measured after a single oral dose administration of 480mg of lumefantrine equal to four tablets of artemether –lumefantrine combination (Exafal). After extraction of lumefantrine with hexane-diethyl ether (70:30v/v) from plasma, it was analysed by HPLC (High performance liquid chromatography) using a C18 reverse phase ODS stainless steel column and a mobile phase of acetonitrile-0.1 M ammonium acetate (90:10, v/v) adjusted to pH 4.9 with ultra violet detection at 335 nm.
Results: The median absorption half-life of lumefantrine was 4.5 hours, with Time to reach peak plasma concentration (Tmax) 8.5 hours, plasma clearance 2.44 l/h and terminal elimination half-life of 89.5 hours. The Mean residence time (MRT) calculated ranged from 62.5 to125.6 (mean 98.17+17.18) hours. The day seven plasma concentrations in all the subjects, less one, were more than the cut-off value of 0.28mg/l required to prevent the recrudescent infection.
Conclusion: The overall pharmacokinetic profile of lumefantrine in Pakistani healthy volunteers appears to be comparable to other ethnic groups reported from various countries and the dose regimen used is adequate for the treatment and prevention of recrudescence.