PHARMACOKINETIC EVALUATION OF LIPOSOMAL ENCAPSULATED AMPICILLIN IN MALE AND FEMALE RATS

The dispositions of free and liposomal entrapped ampicillin were compared in male and female rats after IV administration. Serial blood samples were collected for 2 h in the free drug study and 12 h for the liposomal formulation. Pharmacokinetic parameters obtained with free drug were not significantly different between genders. However, gender significantly influenced the disposition of liposomal encapsulated ampicillin. While no difference was observed in distribution t1/2 between genders, female rats had a shorter MRT, smaller Vss and Vt and faster clearance as compared to male rats. In a second study, spleen, liver, kidney, heart, and lung were harvested post‐injection of free and liposomal entrapped ampicillin. Free ampicillin did not distribute extensively into the tissue compartment and no gender difference was noted. In contrast, liposomal encapsulation resulted in a substantial tissue uptake. In general, female rats had higher concentrations in the spleen and lung as compared to male rats. In vitro plasma stability was not significantly different, suggesting that destabilization of the liposomes does not play a large role in the dispositional differences observed in these studies. However, in vivo interaction of liposomes and plasma lipoproteins may influence the disposition of encapsulated drug. ©1997 by John Wiley & Sons, Ltd.