Utility of gastrointestinal physiology regulated-dogs: bioavailability study of a commercial sustained-release dosage form of theophylline.
The utility of gastrointestinal physiology regulated-dogs (regulated-dogs) was evaluated in a bioavailability study. The gastrointestinal physiology of beagle dogs was regulated with a combined-treatment of intramuscular pentagastrin and intravenous atropine sulfate. Theophylline has been regarded as a drug that is absorbed completely in the entire gastrointestinal tract but slowly in the colon for humans. A commercial sustained-release tablet (SR tablet) of theophylline and a commercial conventional tablet of aminophylline (theophylline hemiethilenediamine salt) were chosen as model preparations in this study. In the regulated-dogs, the drug absorption was almost complete for the conventional tablet. The bioavailability of the SR tablet accounted for 76% in the regulated-dogs and 71% in intact dogs relative to that of the conventional tablet in the regulated-dogs, respectively, but no significant difference was detectable between these values. An advantage of the regulated-dogs over the intact dogs was, however, revealed in the time-profiles of the cumulative percentage of theophylline absorbed from the SR tablet, suggesting a modification of drug absorption by the prolonged arrival of the tablet to the colon.
Sagara
K
K
Research Laboratories, Yoshitomi Pharmaceutical Industries, Ltd., Fukuoka, Japan.
Kawata
M
M
Mizuta
H
H
Shibata
M
M
D000818:Animals; D001682:Biological Availability; D003692:Delayed-Action Preparations; D004285:Dogs / Q000378:metabolism*; D007408:Intestinal Absorption; D008297:Male; D012995:Solubility; D013806:Theophylline / Q000008:administration & dosage / Q000493:pharmacokinetics*
D003692:Delayed-Action Preparations; D013806:Theophylline