What kinds of substrates show P-glycoprotein-dependent intestinal absorption?
Author(s): Ogihara T, Kamiya M, Ozawa M, Fujita T, Yamamoto A, Yamashita S, Ohnishi S, Isomura Y Affiliation(s): Pharmaceutical Research Center, Mochida Pharmaceutical Co., Ltd., Shizuoka, Japan. togihara@mochida.co.jp Publication date & source: 2006-06, Drug Metab Pharmacokinet., 21(3):238-44. Publication type: The influence of P-glycoprotein (P-gp) on intestinal absorption of drugs was investigated by comparison of the uptakes of two P-gp substrates, verapamil and vinblastine, using intestinal segments of wild-type and mdr1a/1b gene-deficient (mdr1a/1b(-/-)) mice, and Caco-2 cells. When [(3)H]vinblastine was injected into intestinal segments of wild-type mice, vinblastine was absorbed from duodenum and ileum, but not from jejunum. This difference among intestinal regions could not be explained by segmental differences of mdr1a mRNA expression. In Caco-2 cells, it was found that vinblastine had a high value of efflux/influx ratio (an index of affinity for P-gp) of 12.1, and a low perm
