M. Weiss et al., EFFECTS OF CARDIAC-OUTPUT ON DISPOSITION KINETICS OF SORBITOL - RECIRCULATORY MODELING, British journal of clinical pharmacology, 41(4), 1996, pp. 261-268
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.