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J Dent

Publications and source records attributed to J Dent.

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The importance of the pylorus as a regulator of solid and liquid emptying from the stomach.

The role of the pylorus in the control of gastric emptying of liquids and digestible solids was investigated in the present study by pylorus excision in six pigs. The pylorus was left intact in another six pigs. Antro-pyloro-duodenal motility was recorded by a sleeve sensor and side holes. Liquid emptying was significantly more rapid in pylorus excised than in pylorus intact animals, during intraduodenal infusion of isosmolar dextrose (712 mL vs 107 mL), fatty acid (402 mL vs 46 mL), amino acids (752 mL vs 112 mL), 25% dextrose (392 mL vs 51 mL) and 3 normal saline (705 mL vs 157 mL). In pylorus excised animals, in contrast to pylorus intact animals, the manometric pattern of isolated pyloric pressure waves at the distal stomach was rarely seen (P < 0.05). In a second series of experiments, pylorus excised animals emptied significantly more (P < 0.04) meat over 120 min (181 g) than pylorus intact animals (80 g), but the proportion of particle sizes emptied was unaltered. In the pig, localized pyloric contractions are important for retardation of gastric emptying when nutrient or hyperosmolar solutions enter the duodenum. By contrast, the pylorus is unimportant in determining the size of solid particles emptied from the stomach.

Animals↗

Pharmacokinetics and metabolism of SK&F 86002 in male and female Sprague-Dawley rats.

Several pharmacokinetic parameters for SK&F 86002 [6-(4'-fluorophenyl)-5-(4'-pyridyl)-2,3-dihydroimidazo(2,1-b)-thia zole] and its metabolites (sulfoxide, sulfone) were measured in male and female Sprague-Dawley rats after iv (5 mg/kg) and a wide range (10-80 mg/kg) of oral doses of SK&F 86002. In both sexes. SK&F 86002 is metabolized to an active metabolite, sulfone, which has an extended half-life (approximately 13 hr) and, therefore, has the potential to accumulate upon repeated dosing. In addition, striking differences between sexes were noted in several of the pharmacokinetic parameters measured. The AUCs areas under the plasma concentration time curves, for SK&F 86002 in female rats obtained at the higher doses of SK&F 86002 were substantially greater than expected, when compared with lower doses in female rats or with equivalent doses in male rats. Furthermore, at all doses of SK&F 86002, AUCs for sulfoxide were substantially larger in female than in male rats. Consequently, the systemic exposure to SK&F 86002 and metabolites is substantially greater in female rats than in male rats. Therefore, extrapolation of the pharmacologic and toxicologic sequelae of SK&F 86002, observed at larger doses in female rats, to lower doses should be approached cautiously. Furthermore, the extended half-life of the pharmacologically active sulfone metabolite of SK&F 86002 suggests that this metabolite could accumulate on repeated daily dosing of SK&F 86002 and could, therefore, account for much of the chronic pharmacologic and toxicologic activity of SK&F 86002.

Animals↗