COMPARATIVE PHARMACOKINETICS OF FREE AND LIPOSOME-ENCAPSULATED AMPICILLIN AFTER INTRAVENOUS AND SUBCUTANEOUS ADMINISTRATIONS

摘要

Pharmacokinetic properties of liposome-encapsulated (LEA) and free (FA) ampicillin after intravenous (IV) and subcutaneous (SC) administrations were compared in sheep. Six healthy adult sheep were used in this study. Ampicillin was encapsulated in multilamellar large vesicles (MLV). FA and LEA were administered at a single recommended dose (5 mg/kg) to the same individual sheep at 1-week interval. Concentrations of the drug in serum were determined by HPLC. Results indicated that, when LEA was administered IV and SC, mean residence time (MRT), elimination half-life (t_(1/2 beta)) and the volume of distribution (V_d) were higher (P<0.05), and clearance (Cl) was lower (P<0.05) than in the case of the free form. When the drug was administered SC, the area under the curve (AUC) and the time to peak concentration (t_(max)) were significantly higher (P<0.05), and maximum concentration (C_(max)) of LEA was lower than those of the free form. The results obtained in the present study shown that liposome encapsulated ampicillin provided the effective and prolonged serum concentration after IV and SC administration.