Pharmacokinetics and bioavailability of oral and intramuscular artemether

Abstract

Objective: The pharmacokinetics and bioavailability of artemether and dihydroartemisinin were investigated in eight Thai males following the administration of single oral and intramuscular doses of artemether (300 mg) in a randomized two-way cross-over study.

Results: Both oral and intramuscular artemether were well-tolerated. In most cases, artemether and dihydroartemisinin were detected in plasma after 30 min and declined to levels below the limit of detection within 18–24 h. Compared with intramuscular administration, oral administration of artemether resulted in a relatively rapid but incomplete absorption [C_max: 474 vs 540 ng · ml⁻¹; t _max: 2.0 vs 3.9 h; AUC: 2.17 vs 5.20 μg · h · ml⁻¹]. Geographic means of lag-time and absorption half-life (t _1/2a) of oral vs intramuscular artemether were 0.28 and 1.1 h vs 0.30 and 2 h, respectively. t _1/2z was significantly shortened after the oral dose [2.8 vs 6.9 h]. Mean oral bioavailability relative to intramuscular administration was 43.2%. The ratio of the AUCs of artemether to dihydroartemisinin was significantly lower after the oral than after the intramuscular dose (geometric mean: 0.29 vs 0.60).