Absence of significant pharmacokinetic and pharmacodynamic interactions between artemether and quinoline antimalarials

The study was carried out to investigate the pharmacokinetic and pharmacody namic interactions between artemether (ARTEM) and quinoline antimalarials n amely mefloquine (MQ), quinine (QN) and primaquine (PQ) when given concurre ntly. A randomised comparative, seven way cross-over design was performed i n eight healthy male Thais following the administrations of seven drug regi mens on seven occasions ie. a single oral dose of ARTEM (300 mg), or MQ (75 0 mg), or QN (600 mg), or PQ (45 mg) alone, or the combination of ARTEM (30 0 mg) with MQ (750 mg), or QN (600 mg), or PQ (45 mg). All clinical and laboratory parameters were normal in all subjects, before, during and after the study. The eight subject experienced no adverse effec t after ARTEM, QN, PQ alone regimens, or combination of ARTEM with QN and P Q. After administration of MQ in either occasion, 3 subjects had weakness, nausea, abdominal pain, and diarrhoea; one subject complained of dizziness. All symptoms were mild and occurred during the first day of MQ administrat ion. The fitting of the concentration-time curves of ARTEM, QN and PQ, to a one- compartment model with first order absorption yielded satisfactory results in all subjects. The best fit model for MQ was two-compartment model with f irst order absorption. The pharmacokinetics of all investigated drug, when given alone or in combination were not significantly different.