Mefloquine concentration profiles during prophylactic dose regimens

A pharmacokinetic study with (malaria) prophylactic doses of mefloquine hyd rochloride was conducted in 12 healthy adult subjects (Caucasians), 6 femal es and 6 males, mean age 29.2 +/- 6.4 years, mean weight 70.6 +/- 13.4 kg. Doses of 250 mg mefloquine were administered on days 0, 1, 7, 14, 21 and 28 . Six subjects received a further 5 weekly doses of 250 mg mefloquine, the others 5 further weekly doses of 125 mg. After the third dose the protectiv e threshold mefloquine concentration in blood plasma was achieved in all su bjects. In female subjects, mean C-min ss, C-max ss and AUC(d 0-35) were si gnificantly higher than in males. After the fifth dose, mean Cmax in female s reached 1692 ng/ml (4.48 mu mol/l), equivalent to a high therapeutic conc entration. This is apparently due to a generally lower body weight and a na rrower volume of distribution in women. Adverse reactions were significantl y more frequent in women than in men. Headache, anorexia, insomnia and vert igo were the most common side effects. The lesser tolerability of mefloquin e in females may be due to the higher drug concentrations in this group. Th is may indicate the need for appropriate adjustment of the prophylactic dos e regimen of mefloquine in females.