PHARMACOKINETIC EVALUATION OF LIPOSOMAL ENCAPSULATED AMPICILLIN IN MALE AND FEMALE RATS

✍ Scribed by ROSELINE L. PARDUE; CATHERINE A. WHITE

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 179 KB
• Volume: 18
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/(sici)1099-081x(199705)18:4<279::aid-bdd989>3.0.co;2-g

✦ Synopsis

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 signi®cantly dierent between genders. However, gender signi®cantly in¯uenced the disposition of liposomal encapsulated ampicillin. While no dierence was observed in distribution t 1/2 between genders, female rats had a shorter MRT, smaller V ss and V t , 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 dierence 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 signi®cantly dierent, suggesting that destabilization of the liposomes does not play a large role in the dispositional dierences observed in these studies. However, in vivo interaction of liposomes and plasma lipoproteins may in¯uence the disposition of encapsulated drug. &1997 by John Wiley & Sons, Ltd.