Divided‐dose kinetics of mefloquine in man.

Abstract

The kinetics of mefloquine was investigated following oral divided-doses in 10 healthy Caucasian volunteers. They received 500 or 750 mg followed by 500 mg 8 h later. Unchanged mefloquine (M) and its carboxylic acid metabolite (MM) were measured in whole blood and plasma for 50 days by h.p.l.c. Maximum blood and plasma M concentrations of 1872 ± 362 ng ml-' (mean ± s.d.) and 1900 ± 434 ng ml-', respectively, were found within 6-10 h after the second dose. The terminal plasma elimination half-life was 20.1 ± 3.7 days (mean ± s.d.) and the oral clearance was 22.3 ± 6.7 ml h-1 kg-1 (mean ± s.d.). Plasma concentrations of MM exceeded those of M by 2-3 fold within 2 days. The whole blood concentration of MM was lower than that in plasma but also exceeded the whole blood concentration of M.

Mefloquine Treatment for Uncomplicated Falciparum Malaria in Young Children 6–24 Months of Age in Northern Ghana

“…17 From this, assuming a 12-hour peak in MQ blood levels, such as that seen in young Thai children, our Day 2 measurement, 36 hours later, might be expected to show the heightened accumulation of CMQ over MQ in Ghanaian children. 31 This was not apparent, however, and even at Day 28, we did not see ratios of CMQ:MQ that approached those of 2-6 that have been reported for adults on weekly prophylaxis. 29,32 The stronger negative correlation we observed on Day 2 between CMQ levels and vomiting was noteworthy, and although our study was not intended or powered to examine the relationship between drug/metabolite levels and clinical condition of these children, no correlation was seen between diarrhea at baseline and blood levels of either MQ or CMQ measured on Day 2.…”

Effects of Mefloquine on the Release of Marker Enzymes from the Rat Liver Crude Lysosomal Fraction

“…Thus, it may be prudent to be cautious if mefloquine is to be used for a prolonged period of time since problems with drug ac cumulation may become prominent in view of its long elimination half-life of 20 days (21 …”

Pharmacokinetics of Mefloquine Combined with Artesunate in Children with Acute Falciparum Malaria

“…Since vomiting and postabsorptive blood levels are major determinants of treatment outcome (16), these data argue in favor of splitting the dose of mefloquine when given alone for the treatment of malaria. In contrast two smaller studies have compared split-and single-dose mefloquine regimens in healthy volunteers and found no difference in the overall bioavailability of mefloquine (4,9). There may also be some benefit in giving mefloquine with food.…”