Urea distribution kinetics analyzed by simultaneous injection of urea and inulin: demonstration that transcapillary exchange is rate limiting.

The kinetics of urea and inulin were studied after simultaneous i.v. injection in six anesthetized dogs. The distribution of both compounds was characterized by a three-compartment model. The initial volume of urea distribution averaged 2.21 +/- 0.39 liters (+/- S.D.) and was similar to the expected volume of intravascular space. Although the 0.66 +/- 0.05 liters/kg of total volume of urea distribution corresponds to total body water, transcapillary exchange between intravascular space and rapid and slow equilibrating interstitial fluid spaces is the rate-limiting step in urea distribution and accounts for the three-compartmental structure of the system used to model the distribution kinetics of both urea and inulin. The free-water diffusion coefficient ratio of urea and inulin and the intercompartment clearances calculated after the simultaneous injection of these compounds were used to estimate blood flows to the fast and slow equilibrating interstitial fluid compartments. The sum of these flows averaged 97% of measured cardiac output (range, 83-113%) and was not significantly different from cardiac output. These studies suggest that the rate of urea removal during dialysis may be affected by hemodynamic factors, as we have shown previously for drugs.