A theoretical investigation has been conducted to understand the decon
volution method used for evaluating the in vivo release rate of an ora
l controlled-release product from the plasma drug concentration versus
time profile. The theory is based on well-accepted pharmacokinetic co
mpartmental models. The cumulative amount of drug released from a dosa
ge form can be partitioned into two parts: the amount already absorbed
and the amount released but still remaining at the absorption site in
the gastrointestinal tract. The cumulative amount absorbed at any tim
e, t, can be estimated from the plasma concentration versus time profi
le by the compartmental model-based Wagner-Nelson method or Loo-Riegel
man method. We have derived a mathematical expression relating the amo
unt at the absorption site with the plasma drug concentration versus t
ime profile assuming a first-order absorption rate process. The differ
ence between the in vivo release profile and the in vivo absorption pr
ofile is illustrated. Because what determined in vitro is the release
profile, it should preferentially be correlated with the in vivo relea
se profile, not the absorption profile. However, when absorption is mu
ch faster than elimination, the estimated absorption profile is a good
approximation of the release profile. In this circumstance, it is adv
antageous to use absorption profiles to demonstrate correlation of in
vitro and in vivo dosage form performance to avoid the noise inherent
in the numerical method of deriving the exact in vivo release profile.