Bioavailability study of commercial sustained-release preparations of diclofenac sodium in gastrointestinal physiology regulated-dogs.
The gastrointestinal (GI) physiology of beagle dogs was regulated with a combined-treatment of intramuscular pentagastrin (10 micrograms/kg x 2) and intravenous atropine sulfate (0.02 mg/kg x 1). Here, the gastric acidity, the gastric emptying time and the small intestinal transit time in the regulated-dogs were respectively around pH 2, 0.7h and 4h, approximating those in healthy humans. The superiority of the regulated-dogs over the intact dogs was confirmed in comparative bioavailability studies by using two classes of commercial preparations. Both the conventional tablet and the sustained-release capsule of diclofenac sodium exhibited simple and similar average plasma concentration-time curves of free diclofenac in the intact dogs, while the latter preparation is reported to reveal a bimodal plasma curve of the drug in healthy humans. The regulated-dogs, however, permitted a bimodal average plasma pattern of the drug for the capsules due to an approximation of the GI physiology between humans and these classes of the dogs. The combined-treatment of beagle dogs with pentagastrin and atropine sulfate seems to supply a useful animal model in predicting the absorption characteristics of the sustained-release preparations and poor water-soluble drugs.
Sagara
K
K
Research Laboratories, Yoshitomi Pharmaceutical Industries, Ltd., Fukuoka, Japan.
Nagamatsu
Y
Y
Yamada
I
I
Kawata
M
M
Mizuta
H
H
Ogawa
K
K
D000818:Animals; D001682:Biological Availability; D003692:Delayed-Action Preparations; D004008:Diclofenac / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004064:Digestive System / Q000187:drug effects*; D004285:Dogs; D005745:Gastric Acidity Determination; D005746:Gastric Emptying / Q000187:drug effects; D005772:Gastrointestinal Transit / Q000187:drug effects; D008297:Male
D003692:Delayed-Action Preparations; D004008:Diclofenac