SIMILARITY OR DISCREPANCY IN PHARMACOKINETIC PARAMETER-ESTIMATION BETWEEN BOLUS AND INFUSION STUDIES

A recent study by Heatherington and Rowland showing discrepancies in s teady-state volume of distribution (V-ss) estimation of two barbiturat es between bolus and infusion studies in rat hindlimb preparations was reviewed Their rationale is that increasing the duration of administr ation may increase the accessibility for tissue distribution and thus increase V-ss for compounds showing slow tissue uptake. Such a dosing- duration-dependent distribution concept is, however, inconsistent with the principle in linear kinetics that the fate or disposition functio n of any drug molecules is independent of time of administration and p resence of other molecules. When their a ell-designed bolus studies we re reanalyzed by including extrapolated outflow data from the last sam pling time to infinity, the V-ss values for the two barbiturates were found to be very similar to those obtained by the infusion method. Our analysis seems to validate a theoretical concept that parameter estim ation is independent of the duration of administration in linear kinet ics. A potential complication of using the bolus method to study V-ss is presented.