Mizuma T, Awazu S
Department of Biopharmaceutics and Drug Rational Research Center, School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-03, Japan.
Biochim Biophys Acta. 1998 Oct 23;1425(2):398-404. doi: 10.1016/s0304-4165(98)00093-2.
Intestinal glucuronidation and absorption of p-nitrophenol (p-NP), acetaminophen (APAP) and 1-naphthol (alpha-NA) in the presence of phloridzin (inhibitor of Na+/glucose cotransporter) and phloretin (aglycone of phloridzin) were studied. Glucuronides of p-NP, APAP and alpha-NA appeared on both the serosal and mucosal sides. The amounts of glucuronides on the serosal side were decreased in the presence of phloridzin and phloretin. p-NP, APAP and alpha-NA appeared on the serosal side as well, and the amounts of p-NP, APAP and alpha-NA on the serosal side were increased by the presence of phloridzin and phloretin. Furthermore, the intestinal glucuronidation and absorption of alpha-NA at various concentrations were studied in the presence and absence of phloretin. Metabolic clearance was decreased in the presence of phloretin, and the absorption clearance was increased. The higher concentrations of alpha-NA caused higher absorption clearance. The lower the metabolic clearance, the higher the absorption clearance. The relationship between glucuronidation metabolism and absorption in intestine was kinetically analyzed by the metabolic inhibition model. Complete inhibition of glucuronidation improved the intestinal absorption of alpha-NA, and the absorption clearance increased to 7.17 microliter/min/cm. The formation of phloretin and an unknown metabolite from phloridzin were observed. An unknown metabolite from phloretin was observed, and was suppressed by the presence of alpha-NA. This suggests that phloridzin was hydrolyzed to phloretin, which was metabolized to glucuronide, and thereby inhibited glucuronidation of p-NP, APAP and alpha-NA.
研究了在根皮苷（钠/葡萄糖共转运体抑制剂）和根皮素（根皮苷的苷元）存在的情况下，对硝基苯酚（p-NP）、对乙酰氨基酚（APAP）和1-萘酚（α-NA）的肠道葡萄糖醛酸化及吸收情况。p-NP、APAP和α-NA的葡萄糖醛酸苷在浆膜侧和黏膜侧均有出现。在根皮苷和根皮素存在的情况下，浆膜侧葡萄糖醛酸苷的量减少。p-NP、APAP和α-NA也出现在浆膜侧，根皮苷和根皮素的存在使浆膜侧p-NP、APAP和α-NA的量增加。此外，研究了在有和没有根皮素存在的情况下，不同浓度α-NA的肠道葡萄糖醛酸化及吸收情况。根皮素存在时代谢清除率降低，吸收清除率增加。α-NA浓度越高，吸收清除率越高。代谢清除率越低，吸收清除率越高。采用代谢抑制模型对肠道葡萄糖醛酸化代谢与吸收之间的关系进行了动力学分析。葡萄糖醛酸化的完全抑制提高了α-NA的肠道吸收，吸收清除率增加到7.17微升/分钟/厘米。观察到根皮苷形成根皮素和一种未知代谢产物。观察到根皮素产生一种未知代谢产物，α-NA的存在可抑制该产物的产生。这表明根皮苷水解为根皮素，根皮素代谢为葡萄糖醛酸苷，从而抑制了p-NP、APAP和α-NA的葡萄糖醛酸化。
