EFFECTS OF CARDIAC-OUTPUT ON DISPOSITION KINETICS OF SORBITOL - RECIRCULATORY MODELING

1 The purpose of this study was to determine the effects of cardiac ou tput on distribution and elimination kinetics of the marker compound s orbitol. 2 The disposition kinetics of sorbitol were investigated afte r rapid intravenous injection and arterial sampling in nine patients w ho had undergone cardiac catheterization whereby the cardiac output wa s measured. 3 A minimal circulatory model consisting of pulmonary and systemic subsystems, both of which were characterized by an inverse Ga ussian transit time density function, fitted the data very well. The m ethod involves numerical inverse Laplace transform of the model equati ons. 4 The mixing clearance introduced as a novel non-compartmental pa rameter of distribution dynamics was significantly correlated with car diac output. The steady-state volume of 14 1 matched the extracellular volume. The systemic extraction ratio of 23% may reflect the fraction al liver blood flow. 5 This pharmacokinetic model can be applied when an independent observation of cardiac output is available. In contrast to the conventional compartmental (or sum of exponential) approach it contains fewer adjustable parameters which can be more readily interp reted in physiological terms.