Model-independent estimation of lag times with first-order absorption and disposition.
The effectiveness of five model-independent procedures for the estimation of lag times (Tlag) was evaluated. Two new methods utilize early concentrations which are weighted by a term exponential in time. They estimate Tlag by weighted linear regression. One of these approaches evaluates also the time when maximum concentration is reached (Tmax). In addition, three older, empirically used procedures are considered. Two methods apply either the first two or three quantifiable concentrations and estimate the lag time by linear regression. Finally, the last unquantifiable concentration is often used as a measure of lag time. Simulations demonstrated that this procedure had large bias and generally high standard deviation. In contrast, the new methods showed small variation and negligible bias. The procedures applying linear regression had intermediate characteristics. Lag times were evaluated effectively by an average of two observations between Tlag and Tmax.
Csizmadia
F
F
Department of Pharmacology, and Department of Preventive Medicine and Biostatistics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Endrenyi
L
L
D001682:Biological Availability; D008954:Models, Biological; D010599:Pharmacokinetics