Key points are not available for this paper at this time.
In 1959, Steele (Ann. N.Y. Acad. Sci. 82, 420–430) suggested a method for measuring the rates of appearance (R a ) and of disappearance (R d ) of a metabolite in an intact system under conditions when R a and R d were changing with time. Steele's method involved modelling the system by a one-compartment model whose effective volume was assumed. To overcome the problem of assuming an effective volume, a model consisting of two compartments rather than one has been postulated. While no distribution volume need now be assumed, a preliminary steady state experiment is required for identification of the coefficients governing exchange of material between the two compartments.In five conscious dogs 14 C-hydroxymethyl inulin (tracer) was infused at a constant rate, while unlabelled inulin (tracee) was infused at varying predetermined rates and the plasma concentrations of both were measured. These were then fitted by a series of smoothly joined polynomials. When the calculated rates of appearance of unlabelled inulin were compared with the actual rates, equally good results were obtained with the one-compartment (using the best effective volume) and the two-compartment models. The calculated values of R d and of the clearance of inulin were not validated experimentally, but their validity is likely since the equations for R d and R a are related, and the R a component has been validated. The identity of unlabelled inulin and the 14 C-hydroxymethyl inulin species was ascertained by gel filtration, and by the identity of their in vivo kinetics.
Norwich et al. (Sat,) studied this question.