An in vivo intestinal perfusion model was used to investigate how experimental hyperglycemia affects intestinal elimination and biliary excretion in the rat. Experimental diabetes was induced by administration of streptozotocin (65 mg/kg, i.v.). The intestinal perfusion medium contained 250 μM (±)-ibuprofen. An isocratic high-performance liquid chromatography method with UV-visible detection was developed to quantitate ibuprofen in the intestinal perfusate, while a gradient method was applied to quantitate ibuprofen and ibuprofen-β-d-glucuronide in the bile. The limit of quantitation of ibuprofen was found to be 0.51 μM in the perfusate of the small intestine. In the bile, the limit of quantitation of ibuprofen and ibuprofen-β-d-glucuronide was 4.42 and 10.3 μM, respectively. Unconjugated ibuprofen and ibuprofen-β-d-glucuronide were detected in the bile; however, no β-d-glucuronide of ibuprofen could be detected in the intestinal perfusate. The results indicate that experimental diabetes can cause a decrease in the disappearance of ibuprofen from the small intestine. Excretion of both ibuprofen and ibuprofen-β-d-glucuronide decreased to the bile in experimental diabetes. The results can be explained by the results of molecular biological studies indicating streptozotocin-initiated alterations in the intestinal and hepatic transport processes.
Keywords: HPLC UV–Vis; STZ-induced hyperglycemia; biliary excretion; chromatographie en phase liquide de haute performance avec détecteur UV-visible; excrétion de la bile; glucuronidation; hyperglycémie engendrée par la streptozotocine; ibuprofen; ibuprofène; intestinal elimination; élimination intestinale.