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Pharm Res. 1995 Apr;12(4):594-8.

Relationship between the phasic period of interdigestive migrating contraction and the systemic bioavailability of acetaminophen in dogs.

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  • 1Research Laboratories, Yoshitomi Pharmaceutical Industries, Ltd., Fukuoka, Japan.


The relationships of the phasic period of interdigestive migrating contraction to gastrointestinal (GI) transit of drugs and their oral absorption were investigated in mongrel dogs by simultaneous oral dosing of acetaminophen (AAP) and salicylazosulfapyridine (SASP) at the starting points of the phase I and phase III periods of gastric contractions. Strain-gauge force transducers were surgically sutured onto the serosa of the GI tracts in the dogs to measure the interdigestive migrating contractions. The mean absorption time of AAP and the time for the first appearance of sulfapyridine (a bacterial metabolite of SASP in the colon) in plasma were used as the indices of gastric emptying time (GET) and small intestinal transit time (SITT), respectively. In individual dogs, the GET and the SITT at phase I showed a clear delay in comparison with those at phase III. For AAP used as a marker compound here, the systemic bioavailability after oral dosing to intact beagle dogs at doses of 3, 10, and 20 mg/kg was about 55, 63, and 79%, suggesting that AAP undergoes a non-linear hepatic clearance. At a dose of AAP 20 mg/kg, the systemic bioavailability of AAP was 100% in the case of dosing at phase III, but was reduced by half when dosing at phase I. These results indicate that, in oral dosing, the transit of drugs through the GI tract was clearly affected by the phases of gastric contractions.(ABSTRACT TRUNCATED AT 250 WORDS)

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