IN-VIVO EVALUATION OF ARTEETHER LIPOSOMES

Arteether is a potent antimalarial agent that is available as oily sol ution intended for intramuscular injection. Liposomal formulation comp osed of dipalmitoylphosphatidylcholine (DPPC), dibehynoyl-phosphatidyl choline (DBPC), cholesterol and arteether in the molar ratio of 1:1:2: 1 was chosen for in vivo evaluation. This composition was found to giv e stable liposomes compared with other formulations and it gave 67.56% trapping efficiency and particle size of 3.21 +/- 0.76 mu m. The lipo somes were administered orally and intravenously to New Zealand rabbit s at a dose of 50 mg/kg. The pharmacokinetic parameters following drug administration were determined in each case. Pharmacokinetic paramete rs 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 a nd 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 o bserved for oral liposomes where relative bioavailability was 97.91% c ompared with 31.83% for the oral suspension. Intersubject variations w ere found to be relatively high in oral liposomes. The obtained values for mean residence time (MRT) and mean absorption time (MAT) indicate d that arteether remains longer in gastrointestinal tract (GIT) with l onger time period for absorption in case of suspension compared with l iposomal formulation. In addition, arteether was successfully administ ered intravenously in liposomal formulations and showed longer elimina tion 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, liposo mal formulation of arteether could allow for intravenous administratio n of the drug in high-risk malaria patients with long duration of effe ct. (C) 1998 Published by Elsevier Science B.V. All rights reserved.