In vivo evaluation of arteether liposomes

Arteether is a potent antimalarial agent that is available as oily solution intended for intramuscular injection. Liposomal formulation composed of dipalmitoylphosphatidylcholine (DPPC), dibehynoyl-phosphatidylcholine (DBPC), cholesterol and arteether in the molar ratio of 1:1:2:1 was chosen for in vivo evaluation. This composition was found to give stable liposomes compared with other formulations and it gave 67.56% trapping efficiency and particle size of 3.21 +/- 0.76 mu m. The liposomes were administered orally and intravenously to New Zealand rabbits at a dose of 50 mg/kg. The pharmacokinetic parameters following drug administration were determined in each case. Pharmacokinetic parameters after oral administration of liposomes were compared with those of oral aqueous suspension of micronized arteether. High bioavailability of arteether was evident in case of oral liposomes where faster rate and better absorption of arteether were observed compared with aqueous suspension. Oral liposomes gave higher C-max and shorter T-max as well as a higher value for AUG. Almost complete arteether absorption was observed for oral liposomes where relative bioavailability was 97.91% compared with 31.83% for the oral suspension. Intersubject variations were found to be relatively high in oral liposomes. The obtained values for mean residence time (MRT) and mean absorption time (MAT) indicated that arteether remains longer in gastrointestinal tract (GIT) with longer time period for absorption in case of suspension compared with liposomal formulation. In addition, arteether was successfully administered intravenously in liposomal formulations and showed longer elimination half-life with respect to other artemisinin derivatives. Thus an optimum oral liposomal formulation for arteether can be developed for fast and complete absorption of the drug from GIT. Furthermore, liposomal formulation of arteether could allow for intravenous administration of the drug in high-risk malaria patients with long duration of effect. (C) 1998 Published by Elsevier Science B.V. All rights reserved.