A single dose pharmacokinetic study of a combined antimalarial formulation of mefloquine, sulphadoxine and pyrimethamine (Fansimef®) has been performed in 10 healthy adult male Malaysian volunteers. The dose consisted of two tablets containing 250 mg mefloquine base, 500 mg sulphadoxine base and 25 mg pyrimethamine base each. Plasma concentrations of mefloquine and pyrimethamine were measured by GC-ECD, those of sulphadoxine by h.p.l.c. Time to peak concentrations (mean ± s.d. for mefloquine (5.70 ± 0.95 h), sulphadoxine (3.75 ± 2.03 h) and pyrimethamine (3.30 ± 1.98 h) were similar to those observed by others after administration of the single compounds. This was also true for elimination half-lives (t½.). The t½/2s for mefloquine, sulphadoxine and pyrimethamine were 387 ± 98 h, 255 ± 61 h and 114 ± 42 h, respectively.

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The hydrochloride, sulphate and ethylcarbonate salts of quinine were given in single oral doses (600 mg base equivalent) to nine healthy male subjects according to a cross-over design. No statistically significant differences were noted in the plasma drug concentrationtime profiles although inter-and intra-subject variation in AUC, Cmax and tmax values was appreciable. The ethylcarbonate salt may be preferred for use in paediatric patients because of its neutral taste.

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Malaria, particularly that due to chloroquine-resistant Plasmodium falciparum, which requires management with antimalarial drugs capable of protecting against multiresistant strains, has emerged in Malaysia. A study was carried out to assess the efficacy and tolerability of 2 dosages of mefloquine/sulfadoxine/pyrimethamine (MSP; RO 13-5112) compared to Fansidar in a malaria endemic area. 914 subjects in 3 random groups were studied. Occurrence of malaria was assessed both clinically as well as by blood films. Plasma drug levels were also measured. The results showed that the low dose of MSP was completely effective in suppressing parasitaemia. 2.7% of the study population reported adverse drug reactions, the lowest incidence being in subjects on the low dose; their blood chemical profiles were also the least affected. The plasma levels of pyrimethamine and sulfadoxine achieved in the low dose group were slightly higher than expected, but there was no significant difference in bioavailability. The study showed that, for chemoprophylaxis, a low dose of MSP provided effective protection with minimal side effects.