Pharmacokinetics of prophylactic mefloquine in Thai healthy volunteers

Malaria constitutes one of the most serious public health problems in Thailand. The disease undermines the health of the people and threatens the economy and security of the country as it is most prevalent in the rural region in forested mountain areas along the border where government officials (border police) have to perform their duties. A safe and effective prophylactic drug for use by these government officials is needed. Nine healthy border police volunteers who were working on the Thai-Cambodia border, aged between 22 to 50 years, and whose weight ranged between 48 and 61 kg, with no history of liver or kidney disease were recruited into the study. 375 mg of mefloquine (as Fansimef tablets) was given as a loading dose, followed by 250 mg every 4 weeks for 4 doses. Whole blood concentrations of mefloquine were measured by high performance liquid chromatography at intervals for 19 weeks. None of the volunteers developed malaria during study period. Seven volunteers had mild adverse effects which required no specific treatment. No changes in liver or renal function or in blood profiles occurred during 19 weeks of observation. Pharmacokinetic analysis revealed a mean maximum concentration of 420 +/- 141 ng/ml a time to peak concentration of 12 +/- 8 hours, terminal half-life was 14.93 +/- 4.43 days, apparent volume of distribution (Vd/f) was 16.5 +/- 5.6 l/kg and total clearance was 0.99 +/- 0.62 ml/min/kg. The mean minimum whole blood mefloquine concentration derived from this study was approximately 100 ng/ml which is considered to be low for treatment.(ABSTRACT TRUNCATED AT 250 WORDS)