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

Abstract

BackgroundA 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.MethodsA 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.ResultsA 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 (Cmax) was 2.53 µg/ml, the area-under-the-curve (AUC0–∞) 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.ConclusionThe 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.

Fixed dose drug combinations – are they pharmacoeconomically sound? Findings and implications especially for lower- and middle-income countries

“…Artemisinin-based combinations or chloroquine in combination with a short course of primaquine have also been shown to be highly effective in the treatment of vivax malaria in Brazil [276]. An FDC of mefloquine combined with artesunate has also been studied in cases of falciparum malaria in the Brazilian Amazon basin and shown to have acceptable efficacy, safety, and tolerability [277]. However, artesunate-mefloquine FDCs have been used infrequently in Africa due to a perceived poor tolerance to mefloquine although recent studies in children in Africa are now suggesting otherwise [278].…”

The Effect of Artemisinin-Based Drugs vs Non-artemisinin-based Drugs on Gametophyte Carrying in the Body After the Treatment of Uncomplicated Falciparum Malaria: A Systematic Review and Meta-analysis

“…The gametophyte carrying rate is high after a large single dose ( Price et al, 1996 ; Rufener et al, 2018 ). Although the combination of MQ and artesunate cannot kill the mature gametophyte, it prevents the development of the gametophyte through the precursor of the sexual stage and thus, improves the tolerance of MQ to partially speed up the recovery of the patients ( Ferreira et al, 2018 ).…”

Structure-switching aptamer sensors for the specific detection of piperaquine and mefloquine

“…An inexpensive assay to detect antimalarial compounds from patient samples and dissolved tablets implemented in malaria clinics or small research laboratories could greatly improve the collection of drug use and quality data. After ACT administration, the long half-life partner drug components are detectable in patient blood samples up to several weeks after treatment, in contrast to artemisinin derivatives and their metabolites, which clear from the blood within a day (30)(31)(32)(33)(34)(35). Piperaquine and mefloquine were selected for detection in this research due to their widespread use and failures against resistant P. falciparum strains in Southeast Asia.…”