Mefloquine concentration profiles during prophylactic dose regimens.

A pharmacokinetic study with (malaria) prophylactic doses of mefloquine hydrochloride was conducted in 12 healthy adult subjects (Caucasians), 6 females 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 protective threshold mefloquine concentration in blood plasma was achieved in all subjects. In female subjects, mean Cmin ss, Cmax ss and AUCd 0-35 were significantly higher than in males. After the fifth dose, mean Cmax in females reached 1692 ng/ml (4.48 mumol/l), equivalent to a high therapeutic concentration. This is apparently due to a generally lower body weight and a narrower volume of distribution in women. Adverse reactions were significantly more frequent in women than in men. Headache, anorexia, insomnia and vertigo were the most common side effects. The lesser tolerability of mefloquine in females may be due to the higher drug concentrations in this group. This may indicate the need for appropriate adjustment of the prophylactic dose regimen of mefloquine in females.