Lf. Lacey et al., EVALUATION OF DIFFERENT INDIRECT MEASURES OF RATE OF DRUG ABSORPTION IN COMPARATIVE PHARMACOKINETIC STUDIES, Journal of pharmaceutical sciences, 83(2), 1994, pp. 212-215
As indirect measures of rate of drug absorption (metrics), maximum pla
sma concentration (C-max) is confounded by extent of drug absorption a
nd the time to reach C-max (t(max)) is a discrete variable, dependent
on blood sampling frequency. Building on the work of Endrenyi at al.,
we have compared different metrics, including C-max/area under the cur
ve of concentration versus time from time zero to infinity (AUC(infini
ty)), partial AUC from zero to t(max), (AUC(p)) and C-max.t(max) with
simulated experiments. Importantly, the performance of these metrics w
as assessed with the results of actual pharmacokinetic studies involvi
ng Glare drugs. The results of the simulated and real experiments were
consistent and produced the following unambiguous findings: (1) C-max
/AUC(infinity) is a more powerful metric than C-max in establishing bi
oequivalence when the formulations are truly bioequivalent; (2) C-max/
AUC(infinity) is more sensitive than C-max at detecting differences in
rate of absorption when they exist; and (3)the treatment ratios for A
UC(p), AUC(p)/AUC(infinity), and C-max.t(max) are very imprecisely est
imated and are of no practical value as measures of rate of absorption
. Of the metrics examined, C-max/AUC(infinity) is the most sensitive a
nd powerful indirect measure of rate of drug absorption in comparative
pharmacokinetic studies involving immediate-release dosage forms and
should be used instead of C-max in bioequivalence testing.