PREDICTION OF THE PLASMA-CONCENTRATION PROFILES OF ORALLY-ADMINISTERED DRUGS IN RATS ON THE BASIS OF GASTROINTESTINAL TRANSIT KINETICS AND ABSORBABILITY
T. Sawamoto et al., PREDICTION OF THE PLASMA-CONCENTRATION PROFILES OF ORALLY-ADMINISTERED DRUGS IN RATS ON THE BASIS OF GASTROINTESTINAL TRANSIT KINETICS AND ABSORBABILITY, Journal of Pharmacy and Pharmacology, 49(4), 1997, pp. 450-457
A new method based on gastrointestinal transit kinetics has been devel
oped for estimation of the absorption profiles of drugs administered o
rally as aqueous solutions. The utility of the method was evaluated in
rats. The gastrointestinal transit profile for each segment was estim
ated by in-vivo studies using phenol red, an unabsorbable marker. The
gastrointestinal transit profile of phenol red was well explained by a
linear gastrointestinal transit kinetic model with eight segments. We
also introduced the absorption process into the gastrointestinal tran
sit kinetic model and the plasma profile was predicted by the convolut
ion method. The absorbability of drugs in each segment was assessed by
an in-situ absorption study. The validity of the model was evaluated
for model drugs with different absorption characteristics. The plasma
profiles predicted for ampicillin, theophylline and cephalexin were in
good agreement with those observed. The overestimated plasma profile
of propranolol suggests that the low bioavailability of propranolol is
a result of first-pass metabolism by the intestine wall and the liver
, because the calculated absolute absorption is almost perfect. This p
roposed model is also suitable for estimation of segmental absorption,
which is useful for the development of drug delivery systems. We have
demonstrated that the plasma profile of orally administered drugs can
be predicted by use of gastrointestinal transit and segmental absorba
bility information and that this method is especially useful for estim
ating separately the effect of absolute absorption and first-pass meta
bolism on the bioavailability of drugs.