PHARMACOKINETIC STUDIES OF IN-SITU LIPOSOMAL PREPARATION CONTAINING AMPHOTERICIN B COMPLEXED WITH DIFFERENT CHEMICALLY MODIFIED beta-CYCLODEXTRINS.
The purpose of this study was to evaluate the influence of chemically modified beta-cyclodextrin (beta-CD) which could affect the in-vivo stabilization of liposomal preparation derived from proliposome entrapping inclusion complex of amphotericin B (AmB) with beta-CD. A series of liposomal AmB formulations with varying beta-CD i.e. Hydroxypropyl beta-CD (HPBCD) & Sulfo butyl ether beta-CD (SBEBCD) and lipid dose having similar AmB content (0.5 mg/kg) were compared with conventional liposomal amphotericin B (L-AmB) or free AmB in rats and their pharmacokinetic data were analyzed considering the varying volume of distribution with respect to the varying lipid concentration (65mg to 110mg) in blood. These results indicate that L-AmB entrapped inclusion complexes safely achieved higher Cmax (P < 0.05) & AUC (P < 0.02) and demonstrated saturable, nonlinear elimination from plasma via reticuloendothelial organ uptake at higher lipid level (>80mg) as compared with conventional L-AmB or free AmB. Furthermore in-vivo stabilization potential for liposomal preparation via AmB/ beta-Cyclodextrin inclusion complexes appeared to be in pattern of HPBCD < SBEBCD. It is concluded that the preparation of liposome derived from proliposome entrapping inclusion complex of amphotericinB (AmB) with beta-CD could serve an alternative approach to enhance the therapeutic window of AmB in clinical medicine.
Chakraborty
K K
KK
Research & Development Division, Hindustan Antibiotics Ltd., Pimpri, Pune, 411 018, India.
Naik
S R
SR