Clinical efficacy and pharmacokinetics of artemisinin monotherapy and in combination with mefloquine in patients with falciparum malaria
Article first published online: 2 OCT 2003
British Journal of Clinical Pharmacology
Volume 41, Issue 6, pages 587–592, June 1996
How to Cite
HASSAN ALIN, M., ASHTON, M., KIHAMIA, C. M., MTEY, G. J. B. and BJÖRKMAN, A. (1996), Clinical efficacy and pharmacokinetics of artemisinin monotherapy and in combination with mefloquine in patients with falciparum malaria. British Journal of Clinical Pharmacology, 41: 587–592. doi: 10.1046/j.1365-2125.1996.35116.x
- Issue published online: 2 OCT 2003
- Article first published online: 2 OCT 2003
- Cited By
- Plasmodium falciparum malaria;
1The aim of this study was to assess the pharmacokinetics, clinical efficacy and safety of artemisinin alone and in combination with mefloquine.
2Thirty-eight adults with symptomatic Plasmodium falciparum malaria were randomly assigned to receive either artemisinin (500 mg single dose followed by another 500 mg on day 1 and then 250 mg twice daily for 4 days) or artemisinin (500 mg single dose followed by 750 mg on day 1 and then 250 mg three times daily for one more day) in co-administration with mefloquine (250 mg three times daily for the first day). All drug administration was by the oral route. Patients were hospitalized at the Kibaha Designated District Hospital, Kibaha, Tanzania, for 6 days and a follow up for 3 weeks was performed.
3Treatment with the artemisinin/mefloquine combination resulted in a shorter parasite clearance time (PCT) of 24 (22, 27; 95% confidence interval) h vs 31 (27, 36) h and fever subsidence time (FST) of 14 (12, 16) h vs 20 (18, 23) h compared with artemisinin monotherapy. The 95% CI for the difference of the PCT and FST were 1.7, 12 and 3, 10, respectively. Parasites were detected in 7 out of 17 patients (41%) receiving artemisinin monotherapy at the 3rd and 4th week follow up visits. No parasites were detected after the combination therapy.
4The maximum plasma concentrations (Cmax) were similar after artemisinin monotherapy (615.4±387.0 ng ml−1) and in combination with mefloquine (851.8±523.6 ng ml−1). Elimination half-lives (t1/2) were also identical at 2.2±0.6 h and 2.5±0.7 h, respectively. However, the AUC values were higher (P<0.05) after combination therapy (3252±1873 ng ml−1 h) than after monotherapy (2234±1502 ng ml−1 h). The oral clearance values were lower (P<0.05) after combination therapy (195.4±86.9 l h−1) than after monotherapy (314.3±189.4 l h−1). PCT and FST normalized to initial parasitaemia correlated with AUC(0, t) (rs=0.56, P=0.02, rs=0.58, P=0.01, respectively) and with Cmax(rs=0.62, P=0.01, rs=0.68, P=0.005, respectively) in the artemisinin monotherapy only.
5One patient on the combination therapy developed a psychiatric condition and two patients on the monotherapy developed skin itch.