Publication: Pharmacokinetics of the four combination regimens of dihydroartemisinin/ mefloquine in acute uncomplicated falciparum malaria
Issued Date
2005-01-01
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ISSN
01251562
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2-s2.0-17744362338
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Mahidol University
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SCOPUS
Bibliographic Citation
Southeast Asian Journal of Tropical Medicine and Public Health. Vol.36, No.1 (2005), 23-33
Suggested Citation
Kesara Na-Bangchang, A. Thanavibul, P. Tippawangkosol, J. Karbwang Pharmacokinetics of the four combination regimens of dihydroartemisinin/ mefloquine in acute uncomplicated falciparum malaria. Southeast Asian Journal of Tropical Medicine and Public Health. Vol.36, No.1 (2005), 23-33. Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/17121
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Title
Pharmacokinetics of the four combination regimens of dihydroartemisinin/ mefloquine in acute uncomplicated falciparum malaria
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Abstract
The pharmacokinetics of oral dihydroartemisinin and mefloquine were investigated in 40 patients (aged 16-30 y, weighing 45-60 kg) with acute uncomplicated falciparum malaria following the four combination regimens of dihydroartemisinin/ mefloquine [regimen-I: 300 mg dihydroartemisinin (h-0) plus 750 mg mefloquine (h-0); regimen-II: 300 mg dihydroartemisinin (h-0) plus 750 mg mefloquine (h-24); regimen-III: 300 mg dihydroartemisinin (h-0) plus 750 and 500 mg mefloquine (h-24 and 30); regimen-IV: 300 mg dihydroartemisinin (h-0) plus 750 and 500 mg mefloquine (h-0, 24)]. The four combination regimens were well tolerated. Patients in all treatment groups had a rapid initial response. However, 9 patients (4, 4, and 1 cases in regimens-I, II, and IV) had reappearance of parasitemia during the follow-up period. Significant changes in the pharmaco-kinetic parameters of both mefloquine and dihydroartemisinin were observed in patients with malaria compared with healthy subjects reported in a paralleled study. For mefloquine, Cmax (mg per dose), AUC 0-day1 (mg per dose), and AUC0-day7 (mg per dose) were significantly higher in patients. Furthermore, tmax, was prolonged while Vz/F contracted and t1/2 z, MRT shortened in patients with malaria. For dihydroartemisinin, Cmax, AUC, t max and Vz/F were changed in the same direction as mefloquine, whereas t1/2z and MRT were prolonged. CL/F was also significantly reduced in patients with malaria. Absorption/disposition kinetics of oral dihydroartemisinin were similar among the various regimens. On the other hand, AUC0-day1 (mg per dose) of mefloquine after regimen-III was significantly higher than the other three regimens. Combination regimens with two divided doses of mefloquine (regimens-III and IV) resulted in a significantly delayed tmax (especially regimens-IV) compared with those with single dose regimens (regimens-I and II).