Formulation and In Vivo Activity of Liposome-Encapsulated Cephapirin

Abstract

Serum levels, tissue distribution, and in vivo activity in mice of two liposomal formulations of cephapirin were compared with those of free cephapirin. Egg phosphatidylcholine (EPC) liposomes containing cephapirin (drug to lipid ratio approximately 1:15 by weight) were relatively stable in serum and provided prolonged serum levels of cephapirin activity after intravenous (iv) administration. With a 200 mg/kg dosage, serum levels were 10 µg/ml or higher for 24 hr after injection. Free drug at a similar dosage is undetectable in 3-5 hr. EPC-cephapirin liposomes showed a protective effect when administered up to 4 hr before infection of mice with Staphylococcus aureus, whereas free drug had no effect when given prophylactically. Cephapirin liposomes prepared with the tris salt of cholesterol hemisuccinate (CHS-t) were not stable in serum, but provided prolonged serum levels of cephapirin when injected subcutaneously and resulted in a protective effect when given prophylactically to mice infected with S. aureus. Cephapirin activity in the spleen and liver was greatly increased and persisted for at least 24 hr in mice injected intravenously with EPC formulation, but were not increased with the CHS-t formulation given subcutaneously. Only the EPC formulation could prolong survival in mice infected with Salmonella typhimurium.