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.

Persistence of protective immunity following vaccination against tick-borne encephalitis--longer than expected?

A descriptive evaluation of protective immunity was performed on subjects with a complete primary tick-borne encephalitis (TBE) immunization (and additional regular boosters) more than 3 years after primary or booster TBE immunization, as measured by neutralization test and two different ELISA systems. The study population (n = 430) was stratified for age (i.e., 18-49 or 50 years of age) and for the number of years since last TBE vaccination. GMTs (NT) of all subgroups (at the time of the present evaluation) were above detection limit: 144 and 44 for the 18-49- and 50-year-old subjects, respectively. One percent of subjects aged 18-49 years, and 6% of subjects aged 50 years were ELISA-negative. A detailed sub analysis revealed that subjects with either low NT and/or negative to borderline ELISA test results are usually older and constitute a higher number of subjects without any TBE booster vaccination compared to the respective test-positive subject group. From the fourth year (exceeding 3 years after last vaccination) titers show a decline rate of 6-7%. This study indicates that after multiple TBE (booster) immunizations protection surpasses the currently advised TBE booster interval of 3 years, thus supporting reconsideration of the recommendations for booster intervals.