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.

The clinical effectiveness of the standard regimen of chloroquine (CQ) (a total dose of 1500 mg, given over 48 h at 0, 6, 24 and 48 h) for the treatment of Plasmodium vivax malaria in Thailand was investigated in 57 patients in an endemic area of Thailand (Chantaburi Province, eastern Thailand). For radical treatment, an additional course of a tissue schizontocidal agent, primaquine, was given following the complete course of CQ. With this regimen, satisfactory whole blood concentration-time profiles of CQ and its major metabolite desethylchloroquine (DECQ) were achieved. Mean whole blood levels of CQ and DECQ always much exceeded the reported therapeutic level of CQ (90 ng/mL) during the first 7 d of treatment. All patients responded well to the treatment; in most cases, complete and rapid clearance of parasitaemia was observed within the first 48 h. No reappearance of the parasitaemia was detected in peripheral blood films of any patient within 14 d of the evaluation period. In 6 patients, however, reappearance of P. vivax parasitaemia was observed after 30 d; 2 of them had not completed the course of primaquine. There was no difference in whole blood concentrations of CQ and DECQ, admission parasitaemia, susceptibility of the isolates to chloroquine in vitro, and parasite clearance time between patients with or without reappearance of parasitaemia. A prominent trend of deteriorating sensitivity of the parasite to the drug was, however, suggested.

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.