PHARMACOKINETICS OF MEFLOQUINE, WHEN GIVEN ALONE AND IN COMBINATION WITH ARTEMETHER, IN PATIENTS WITH UNCOMPLICATED FALCIPARUM-MALARIA

The pharmacokinetics of mefloquine at a single oral dose of 750 mg, wh en given alone or 24 hours after a single oral dose of artemether (300 mg) was investigated in 27 Thai patients with acute uncomplicated fal ciparum malaria (17 with mefloquine alone, 10 with the combination). T he oral bioavailability of mefloquine was significantly decreased when administered 24 hours after an oral dose of artemether. This was evid ent by the significantly lower values of C-max, AUC[0-24 h], AUC[0-48 h], AUC[0-72 h], as well as total AUC[C-max: 1,290 (827-2,619) vs 1,82 0 (1,283-2,531) ng . ml(-1); AUC[0-24 h]: 0.99 (0.64-1.41) vs 1.33 (1. 07-1.95) mu g . day . ml(-1); AUC[0-48 h]: 1.78(1.23-2.58) vs 2.67 (2. 09-3.84) mu g . day . ml(-1); AUC[0-72 h]: 2.74 (1.63-3.6) vs 4.54 (2. 88-5.38) mu g . day . ml(-1); AUC: 11.11 (6-20.96) vs 15.29 (9.3-36.71 ) mu g . day . ml(-1)]. T-max was also delayed with the combination re gimen [14 (5-24) vs 6 (4-16) h]. Terminal elimination half-lives were comparable [t(1/2z): 11.1 (6.8-14.3) vs 13.4 (10.5-19.1) h].