PHARMACOKINETICS OF PENICILLIN-G IN PLASMA AND INTERSTITIAL FLUID COLLECTED WITH DIALYSIS FIBER-BUNDLES IN SHEEP

A new method of collection of interstitial fluid (ISF) (the site of mo st bacterial infections) was developed for the determination of free ( unbound) penicillin G concentrations in sheep. Dialysis fiber bundles for the collection of ISF were first characterized in vitro and subseq uently implanted in the subcutaneous fascia of the dorsal thorax paral lel to the vertebral column in sheep. The sheep were then dosed intrav enously with 26.4 and 52.9 mg/kg of sodium penicillin G using a crosso ver experimental design. Plasma and ISF dialysate were collected after dosing for determination of penicillin G concentrations using high pr essure liquid chromatography (HPLC), The concentration of penicillin G in the ISF dialysate was calculated with the recovery ratio determine d for each fiber bundle. The decline of penicillin G concentrations in ISF dialysate paralleled the disappearance of the drug from plasma pr oviding evidence for the rapid diffusion of penicillin G into the fibe r bundles. Pharmacokinetic analysis determined that the disposition of penicillin G was best described by a two-compartment open model with penicillin concentrations in plasma (Cp) defined by two biexponential equations, Cp = 170.64e(-716t) + 31.04e(-1.56t) for the low dose and C p = 418.19e(-6.15t) + 59.85e(-1.56t) for the high dose.