Sagara K, Mizuta H, Ohshiko M, Shibata M, Haga K
Research Laboratories, Yoshitomi Pharmaceutical Industries, Ltd., Fukuoka, Japan.
Pharm Res. 1995 Apr;12(4):594-8. doi: 10.1023/a:1016270417009.
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)
通过在胃收缩的I期和III期起始点同时口服对乙酰氨基酚（AAP）和柳氮磺胺吡啶（SASP），在杂种犬中研究消化间期移行性收缩的时相期与药物胃肠道（GI）转运及其口服吸收之间的关系。将应变片式力传感器手术缝合到犬胃肠道的浆膜上，以测量消化间期移行性收缩。AAP的平均吸收时间和磺胺吡啶（SASP在结肠中的细菌代谢产物）在血浆中首次出现的时间分别用作胃排空时间（GET）和小肠转运时间（SITT）的指标。在个体犬中，I期的GET和SITT与III期相比明显延迟。对于此处用作标记化合物的AAP，以3、10和20mg/kg的剂量口服给药给完整的比格犬后，其全身生物利用度分别约为55%、63%和79%，表明AAP经历非线性肝清除。在AAP剂量为20mg/kg时，在III期给药时AAP的全身生物利用度为100%，但在I期给药时降低了一半。这些结果表明，在口服给药时，药物通过胃肠道的转运明显受胃收缩阶段的影响。（摘要截断于250字）
