The pharmacokinetics of mefloquine when given alone or in combination with sulphadoxine and pyrimethamine in Thai male and female subjects

Abstract

The kinetics of mefloquine were studied in 12 healthy Thai male and 12 healthy Thai female volunteers. Mefloquine (MQ) was administered either alone (750 mg orally) or in combination (MSP) with sulphadoxine (1.5 g) and pyrimethamine (75 mg) to each of 6 male and 6 female subjects. Plasma concentrations of MQ were measured by HPLC at intervals for 42 days. There was considerable interindividual variability in the pharmacokinetic parameters; for example in the male subjects receiving MQ alone peak concentrations ranged between 638 and 2494 ng·ml⁻¹ with a mean concentration of 1442 ng·ml⁻¹. Compared to previously published data on MQ concentrations in Caucasian male subjects, the present study indicates that higher concentrations are achieved in Thai subjects. The only significant difference in kinetic parameters between male and female subjects receiving MQ alone was in the mean residence time (MRT) which was greater in females. However, an analysis of pharmacokinetic parameters following administration of the combination preparation showed that the time to peak (t_max) was significantly reduced in females receiving MSP compared to the corresponding females given MQ alone and males given MSP. When data obtained from all subjects (male and female) receiving either MQ alone or MSP were combined, both MRT and half-life were significantly greater in subjects given MSP. There is therefore some evidence that therapeutic concentrations of MQ are maintained for a longer period of time following MSP administration.