Distribution of cephapirin into a tissue chamber implanted subcutaneously in horses

The pharmacokinetics of cephapirin sodium and its distribution into a tissue chamber implanted subcutaneously in the neck of mature horses are described. Cephapirin was administered as an intravenous bolus dose of 20 mg/kg. The serum concentration vs time curve was best described by a two-compartment open model. Cephapirin disappeared from serum rapidly (t1/2 beta = 18.8 min), and had only a modest volume of distribution (Vd(area) approximately equal to 346 mg/kg, Vd(ss) approximately equal to 204 ml/kg). Total clearance was also rapid (approximately equal to 13 ml/min.kg). Concentrations of the antibiotic in tissue chamber fluid, however, were quite constant from 30 min to 3 h post-injection, and did not decay in parallel with either the concentration of the drug in serum or the estimated concentration of drug in the peripheral compartment. The ratio of area under the curve (AUC0-3 h) for serum: chamber fluid was 13.8 : 1, while that for peripheral compartment : chamber fluid was 11 : 1. The slow rate of cephapirin transport into, and out of, the chamber may be related to its hydrophilic nature. The lack of parallelism between the chamber fluid decay curve and that of serum is characteristic of drugs with a very short half-life.