One hundred and two Thai patients with severe falciparum malaria (92 males and 10 females) were allocated at random to receive either the standard regimen of quinine infusion (52 cases) or intramuscular artemether (50 cases). The patients in both groups had comparable admission clinical and laboratory data. Artemether gave a better survival rate (87.2% vs. 63.3%) and parasite clearance time (54 vs. 78 h) than quinine. Fever clearance times (79 h vs. 84 h) and time to recovery of consciousness (48 h in both groups) were comparable. Previous treatment with quinine or mefloquine had no influence on treatment outcome. The most common adverse effect in patients treated with quinine was tinnitus. Two patients had severe hearing impairment which resolved within 1 week after the end of treatment. Mild, transient pain was noted at the injection site of artemether but no abscess formed. QTc wave prolongation was seen in most patients receiving quinine; however, no arrhythmia was observed despite the high concentration of quinine in some patients who had received quinine before admission. Complications developed in 7 survivors in each treatment group. No patient in the artemether group had neurological sequelae after recovery of consciousness, but 2 in the quinine group had left facial palsy and one had a myasthenia gravis-like syndrome. No patient died with complications in he artemether group, but 7 died with pulmonary complications in the quinine group.

AimsThe pharmacokinetics of intramuscular artemether and its major plasma metabolite-dihydroartemisinin, were investigated in patients with severe manifestations of falciparum malaria. Methods Six severe falciparum malaria patients with acute renal failure (ARF) and 11 without ARF were recruited into the study. They were treated with intramuscular artemether at a loading dose of 160 mg, followed by daily doses of 80 mg for another 6 days (total dose 640 mg). Results Patients with and without ARF showed a good initial response to treatment; the parasite and fever clearance times were 66(30-164) and 76(36-140) h [median(range)], respectively. None had reappearance of parasitaemia in their peripheral blood smear within 7 days of initiation of treatment. In comatose patients, the time to recovery of consciousness was 51.6(22-144) h. Artemether was detected in plasma as early as 1 h after a 160 mg dose, and declined to undetectable levels within 24 h in most cases. Patients with ARF had significantly higher C max [2.38(1.89-3.95) vs 1.56(1.05-3.38) ng ml Conclusions ARF significantly modified the pharmacokinetics of intramuscular artemether. The changes could be attributed to either improved absorption/ bioavailability, a reduction of systemic clearance, or a change in plasma protein binding of the drug.

SummaryPlasma quinine (Qn) monitoring was performed in 32 patients with severe falciparum malaria (10 with acute renal failure (ARF) and 2 2 with other severe manifestations) who were treated with the standard regimen of 10 mg/kg body weight Qn dihydrochloride, with a loading dose of 20 mg/kg body weight. Median plasma Q n concentrations prior to the first dose on each day were approximately 10-30% higher in ARF patients than in non-ARF patients during acute infection. Seven patients underwent haemodialysis; 2 died after 2