Pharmacokinetics of mefloquine administered with artesunate in patients with uncomplicated falciparum malaria from the Brazilian Amazon basin.

Autor: Ferreira MVD; Pharmacy Faculty, Pará Federal University, Augusto Correa Street 01, Campus Universitário do Guamá, Belém, Pará, Brazil., Vieira JLF; Pharmacy Faculty, Pará Federal University, Augusto Correa Street 01, Campus Universitário do Guamá, Belém, Pará, Brazil. jvieira@ufpa.br., Almeida ED; Pharmacy Faculty, Pará Federal University, Augusto Correa Street 01, Campus Universitário do Guamá, Belém, Pará, Brazil., Rivera JGB; Pharmacy Faculty, Pará Federal University, Augusto Correa Street 01, Campus Universitário do Guamá, Belém, Pará, Brazil., Gomes MSM; Laboratory of Public Health of Macapa, Av. Adilson José Pinto Pereira, 907, Macapá, Amapá, Brazil., de Siqueira AM; Fiocruz, Av. Brasil, Manguinhos, Rio De Janeiro, Brazil.
Jazyk: angličtina
Zdroj: Malaria journal [Malar J] 2018 Jul 16; Vol. 17 (1), pp. 268. Date of Electronic Publication: 2018 Jul 16.
DOI: 10.1186/s12936-018-2416-0
Abstrakt: Background: A fixed-dose combination of mefloquine with artesunate was evaluated in cases of falciparum malaria in the Brazilian Amazon basin with acceptable efficacy, safety and tolerability. However, there are no data on the pharmacokinetics of mefloquine in this coformulation in Brazil, which is valuable to evaluate whether Plasmodium is exposed to an effective concentration of the drug.
Methods: A prospective, single-arm study was conducted in male patients with slide-confirmed infection by Plasmodium falciparum using two tablets of a fixed-dose combination of artesunate (100 mg) and mefloquine base (200 mg) once daily and over 3 consecutive days. Serial blood samples were collected at admission and throughout 672 h post-administration of the drugs. Mefloquine was measured in each blood sample by high-performance liquid chromatography. The pharmacokinetic parameters were determined by non-compartmental analysis.
Results: A total of 61 patients were enrolled in the study and 450 whole blood samples were collected for mefloquine measurement. The mefloquine half-life was 10.25 days, the maximum concentration (C max ) was 2.53 µg/ml, the area-under-the-curve (AUC 0-∞ ) was 359 µg / ml h, the observed clearance (Cl/f) was 0.045 l/kg/h and the volume of distribution (V/f) was 14.6 l/kg. Mefloquine concentrations above 0.5 µg/ml were sustained for a mean time of 9.2 days.
Conclusion: The pharmacokinetic parameters of mefloquine determined in the study suggest an adequate exposure of parasite to mefloquine in the multiple oral dose regimen of the fixed dose combination of mefloquine and artesunate.
Databáze: MEDLINE
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