The rate of elimination and distribution volume of rabbit muscle creatine phosphokinase.

Abstract

An in vivo study on the elimination of rabbit muscle creatine phosphokinase (CPK) following intravenous administration has been carried out with nine rabbits selected for low endogeneous CPK fluctuation character. A two-compartment open model is proposed for the disposition of CPK. The equation Cp=Ae-α1+Be-β1 was employed to fit the profile of CPK activity in the plasma. The pharmacokinetic parameters of CPK in rabbits were determined at low, medium and high dose levels, and the factors which affect the estimation of pharmacokinetic parameters are discussed. The elimination of CPK appeared to be independent of the injected dose, but the intersubject variability was significant. The pharmacokinetic parameters α and β at high injected dose (860 U/kg body weight, n=9) were estimated to be 0.432±0.274 h-1 and 0.099±0.031 h-1. This value for β in vivo is significantly larger than the inactivation rate constant of CPK in vitro. Hence, there must be some other mechanism involved in vivo in addition to simple inactivation in the circulation by the body temperature. The distribution volume of injected CPK in the steady state was estimated to be approximately 4.3±1.1% of body weight. The result suggests that injected CPK is distributed into a major compartment (plasma) and a minor one (assumed to be interstitium).