Acetylcholine (ACh)-induced membrane currents were investigated using freshly isolated endothelial layers prepared from the guinea-pig mesenteric artery. Gap junctions were blocked by mefloquine and the whole-cell patch clamp method was applied to individual endothelial cells within each multicellular preparation. While mefloquine effectively blocked the gap junctions, it hyperpolarized the mem...

Chemotherapy is a critical component of malaria control. However, the most deadly malaria pathogen, Plasmodium falciparum, has repeatedly mounted resistance against a series of antimalarial drugs used in the last decades. Southeast Asia is an epicenter of emerging antimalarial drug resistance, including recent resistance to the artemisinins, the core component of all recommended antimalarial co...

BACKGROUND Artemisinin-combination therapy (ACT) is recommended as first-line treatment of falciparum malaria throughout the world, and fixed-dose combinations are preferred by WHO; whether a single gametocytocidal dose of primaquine should be added is unknown. We aimed to compare effectiveness of four fixed-dose ACTs and a loose tablet combination of artesunate and mefloquine, and assess the a...

Chronic Schistosoma mansoni infections lead to severe tissue destruction of the gut wall and liver and can influence drug disposition. This study aimed to investigate the impact of a chronic S. mansoni infection on the pharmacokinetic (PK) parameters of two promising antischistosomal lead candidates (mefloquine and enpiroline) in mice. Studies were conducted in two different mouse cohorts (S. m...

OBJECTIVES Previous studies of a fixed combination including cotrimoxazole, rifampicin, and isoniazid (Cotrifazid) showed efficacy against resistant strains of Plasmodium falciparum in animal models and in small-scale human studies. We conducted a multicentric noninferiority trial to assess the safety and efficacy of Cotrifazid against drug-resistant malaria in Papua New Guinea. DESIGN The tr...

Introduction extensive and mefloquine is not detectable in the CSF. The drug is very slowly eliminated, mainly as a carboxylic acid metabolite, with a half-time of about 1 Falciparum malaria remains one of the world’s biggest killers, accounting for about 2.1 million deaths in 1995— month. It is excreted in breast milk [2]. Mefloquine is effective against many isolates of about 4% of all global...

Resistance to antimalarial drugs is a public health problem worldwide. Molecular markers for drug-resistant malaria, such as pfcrt and pfmdr1 polymorphisms, could serve as useful surveillance tools. To evaluate this possibility, sequence polymorphisms in pfcrt (position 76) and pfmdr1 (positions 86, 184, 1034, 1042, and 1246) and in vitro drug sensitivities were measured for 65 Plasmodium falci...

Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release solid oral dosage forms containing mefloquine hydrochloride as the only active pharmaceutical ingredient (API) are reviewed. The solubility and permeability data of mefloquine hydrochloride as well as its therapeutic use and therapeutic index, its pharmacokinet...

Mefloquine has been one of the more valuable antimalarial drugs but has never reached its full clinical potential due to concerns about its neurologic side effects, its greater expense than that of other antimalarials, and the emergence of resistance. The commercial development of mefloquine superseded that of another quinolinyl methanol, WR030090, which was used as an experimental antimalarial...

The bioavailability/pharmacokinetics of dihydroartemisinin and mefloquine following the oral doses of 4 mg/kg body weight artesunate (Cambodian Pharmaceutical Enterprise) given concurrently with 10 mg/kg body weight oral mefloquine artesunate (Cambodian Pharmaceutical Enterprise) were investigated in 15 healthy Cambodian male volunteers. Both formulations were generally well tolerated. Both pro...