Interstitial diffusion and accumulation of cephalothin according to various modes of intermittent administration to rabbits

Abstract

In order to study the effect of different methods of administration of cephalothin, we have used an animal model in which antibiotic concentrations could be studied in an extravascular site. Interstitial fluid (IF) was obtained in rabbits from subcutaneous silastic tissue cages. A 30 mg/kg dose of cephalothin was administered through i.m. injections, 1 h i.v. infusion, 0.25 h i.v. infusion and bolus injection. For each method, 5 rabbits received 3 administrations (one every 3 h). When compared 3 h after the second and the third injection, IF cephalothin concentrations appeared to be significantly higher after 0.25 h infusions than after the other modes of administration (P > 0.001). IF levels following 1 h infusions and bolus injections were not significantly different. With all 3 i.v. methods of administration, a significant cumulative effect was noted in IF but not in serum. Our data suggest, for each chosen period and dose, the existence of an optimal infusion time which would give the highest drug accumulation in IF.