SIMULTANEOUS ANALYSIS OF INSULIN AND N-15(2)-UREA KINETICS IN HUMANS

To elucidate the physiologic basis of multicompartmental systems used to model drug distribution, we studied inulin and N2-(N-15)-urea kinet ics after simultaneous intravenous injection in five normal subjects. Distribution of both compounds was characterized by three-compartment models in which the central compartment corresponded to intravascular space. The mean distribution volumes of 0.164 +/- 0.009 L/kg (+/- SD) for inulin and of 0.670 +/- 0.143 L/kg for urea were similar to expect ed values for extracellular space and total body water, respectively. Distribution from intravascular space was kinetically heterogeneous, p resumably reflecting differences in vascular beds supplied by either f enestrated and discontinuous capillaries or capillaries with a continu ous basement membrane. Intercompartmental clearances of inulin and ure a and the ratio of their free water diffusion coefficients were used t o estimate blood flows and permeability coefficient-surface area produ cts for the peripheral compartments. The sum of compartmental blood fl ows averaged 5.39 +/- 0.49 L/min and was similar to dual-beam Doppler measurements of cardiac output (5.47 +/- 0.40 L/min).