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, when given alone or 24 hours after a single oral dose of artemether (300 mg) was investigated in 27 Thai patients with acute uncomplicated falciparum malaria (17 with mefloquine alone, 10 with the combination). The oral bioavailability of mefloquine was significantly decreased when administered 24 hours after an oral dose of artemether. This was evident 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 1,820 (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 regimen [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].