Preliminary in vivo studies of a new lecithin-based formulation of paclitaxel.
Amorphous paclitaxel dissolves rapidly (1 mg mL(-1)) in an isotonic aqueous dispersion of egg lecithin (5% w/w), a new biocompatible submicron drug carrier consisting of structured aggregates with average size 0.5 microm. The solution is physically stable for at least 24 h and can be administered as an intravenous infusion. After a 5 h infusion in rabbits (0.66 mg kg(-1) h(-1)), changes in blood morphology were comparable to those observed in rabbits that received the commercial product Taxol. No changes in the enzyme profiles (alanine/aspartate aminotransferase or alkaline phosphatase) were observed. However, during infusion of the new formulation plasma concentration of paclitaxel (292 +/- 182 ng mL(-1)) was lower than observed after Cremophor-containing Taxol (540 +/- 262 ng mL(-1)). This result may indicate that the tissue distribution is different for the two drug formulations. Daily intraperitoneal administrations (3 doses/day) in mice demonstrated that the new carrier solution was non-toxic and, relative to Taxol, the new formulation exhibited similar or less toxicity.
Department of Pharmaceutical Technology, Medical University of Gdansk, Gdansk, Poland. msznito@amg.gda.pl
Malgorzata
M
Sznitowska
Malgorzata
M
Bodnar
Jacek
J
Petrusewicz
Helena
H
Janik
Ewa Anna
EA
Dabrowska
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical; D005260:Female; D054709:Lecithins / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D017239:Paclitaxel / Q000737:chemistry* / Q000494:pharmacology; D011817:Rabbits
D000972:Antineoplastic Agents, Phytogenic; D054709:Lecithins; D017239:Paclitaxel