Monoexponential extrapolation of tracer clearance curves in kinetic analysis.

Kinetic analysis of inert tracers shows that some of the most important parameters such as the average turnover rate and the total volume of distribution can be calculated only if the entire time course of the tracer clearance is known. This means that extrapolation beyond the observation period (to infinity) must necessarily be accomplished. This paper presents arguments to support the monoexponential extrapolating function which often is used without justification. The arguments show that one cannot in the general case assign any clearcut physical value to the intercept or exponential coefficient of the extrapolating function. Theoretically, a monoexponential tail of a tracer clearance curve obtained from a system in a steady state is reached when the slope of the curve is proportional to the curve. Under certain conditions this slope can be measured as an independent observation, and hence the monoexponentiality can be put to a fairly rigorous experimental test. This concept is illustrated by clearance studies of Cr-EDTA and Ithalamate from the isolated cat gastrocnemius muscle. Furthermore, it is demonstrated that monoexponential extrapolation as made before the appearance of the final exponential part of the outflow curve can cause considerable error in determination of the mean transit time and hence of the volume of distribution for the tracer. Even with an apparent recovery of the tracer of about 99.7*, the mean transit time was underestimated by 20%.