Publication: Pharmacokinetics and bioequivalence evaluation of three commercial tablet formulations of mefloquine when given in combination with dihydroartemisinin in patients with acute uncomplicated falciparum malaria
Issued Date
2000-01-01
Resource Type
ISSN
00316970
Other identifier(s)
2-s2.0-0033956599
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
European Journal of Clinical Pharmacology. Vol.55, No.10 (2000), 743-748
Suggested Citation
K. Na-Bangchang, J. Karbwang, P. A.C. Palacios, R. Ubalee, S. Saengtertsilapachai, W. H. Wernsdorfer Pharmacokinetics and bioequivalence evaluation of three commercial tablet formulations of mefloquine when given in combination with dihydroartemisinin in patients with acute uncomplicated falciparum malaria. European Journal of Clinical Pharmacology. Vol.55, No.10 (2000), 743-748. doi:10.1007/s002280050008 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/26341
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Pharmacokinetics and bioequivalence evaluation of three commercial tablet formulations of mefloquine when given in combination with dihydroartemisinin in patients with acute uncomplicated falciparum malaria
Other Contributor(s)
Abstract
Objective: To assess the pharmacokinetics and relative bioavailability/bioequivalence of three commercial tablet formulations of mefloquine, i.e. Lariam (reference formulation), Mephaquin 100 Lactab and Eloquin-250, when given sequentially after dihydroartemisinin in Thai patients with acute uncomplicated falciparum malaria. Methods: Twenty-nine Thai patients with acute uncomplicated falciparum malaria were randomized to receive an initial dose of 300 mg dihydroartemisinin, followed by 1250 mg mefloquine (at 24 h and 30 h after dihydroartemisinin) given as either Lariam (n = 10 cases), Mephaquin (n = 9 cases) or Eloquin-250 (n = 10 cases). Serial blood samples were obtained up to day 42 after treatment with mefloquine. Mefloquine concentrations were determined in whole blood by means of ultraviolet high-performance liquid chromatography. The pharmacokinetic parameters of mefloquine were estimated using non-compartmental and compartmental analysis. Results: The three combination regimens were well tolerated. Patients in all treatment groups had a rapid initial response. However, nine patients (four and five cases in regimen containing Mephaquin 100 Lactab and Eloquin-250, respectively) had reappearance of parasitaemia during the follow-up period. Mefloquine from the three formulations showed significantly different pharmacokinetic and bioavailability metrics. Significantly lower peak plasma concentrations (C(max)) and areas under the plasma concentration-time curve (AUC; AUC(0-48h), AUC(0-7days), and total AUC) were observed with Mephaquin 100 Lactab than with the other two formulations. Mean values for relative bioavailability of the test to standard products were 49.1% (Mephaquin 100 Lactab) and 72.4% (Eloquine-250). Based on the criteria set, the bioavailability of the two test products (Mephaquin 100 Lactab and Eloquine-250) was considered non-equivalent to the reference product with respect to the rate (t(max), C(max)) and extent (AUC(0-48h), AUC(0-7days), total AUC) of mefloquine absorption.