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Role of intestinal efflux transporters in the intestinal absorption of methotrexate in rats.
J Pharm Pharmacol. 2007 Sep; 59(9):1263-70.JP

Abstract

The role of intestinal efflux transporters such as P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and multidrug resistance-associated proteins (MRPs) in intestinal absorption of methotrexate was examined in rats. In everted intestine, the mucosal efflux of methotrexate after application to serosal side was higher in jejunum than ileum, and the efflux in jejunum was suppressed by pantoprazole, a BCRP inhibitor, and probenecid, an MRP inhibitor, but not by verapamil, a P-gp inhibitor. The mucosal methotrexate efflux in ileum was suppressed by pantoprazole, but not by other inhibitors. On the other hand, the serosal efflux of methotrexate after application to mucosal side was greater in ileum than jejunum, and was suppressed by probenecid. In in-vivo rat studies, the intestinal absorption of methotrexate was significantly higher when methotrexate was administered to ileum than jejunum. Pantoprazole increased methotrexate absorption from jejunum and ileum. Probenecid increased the absorption of methotrexate from jejunum but decreased the absorption from ileum, as evaluated by peak plasma methotrexate levels. In conclusion, BCRP and MRPs are involved in the regional difference in absorption of methotrexate along the intestine, depending on their expression sites.

Authors+Show Affiliations

Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17883898

Citation

Yokooji, Tomoharu, et al. "Role of Intestinal Efflux Transporters in the Intestinal Absorption of Methotrexate in Rats." The Journal of Pharmacy and Pharmacology, vol. 59, no. 9, 2007, pp. 1263-70.
Yokooji T, Murakami T, Yumoto R, et al. Role of intestinal efflux transporters in the intestinal absorption of methotrexate in rats. J Pharm Pharmacol. 2007;59(9):1263-70.
Yokooji, T., Murakami, T., Yumoto, R., Nagai, J., & Takano, M. (2007). Role of intestinal efflux transporters in the intestinal absorption of methotrexate in rats. The Journal of Pharmacy and Pharmacology, 59(9), 1263-70.
Yokooji T, et al. Role of Intestinal Efflux Transporters in the Intestinal Absorption of Methotrexate in Rats. J Pharm Pharmacol. 2007;59(9):1263-70. PubMed PMID: 17883898.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of intestinal efflux transporters in the intestinal absorption of methotrexate in rats. AU - Yokooji,Tomoharu, AU - Murakami,Teruo, AU - Yumoto,Ryoko, AU - Nagai,Junya, AU - Takano,Mikihisa, PY - 2007/9/22/pubmed PY - 2008/1/9/medline PY - 2007/9/22/entrez SP - 1263 EP - 70 JF - The Journal of pharmacy and pharmacology JO - J Pharm Pharmacol VL - 59 IS - 9 N2 - The role of intestinal efflux transporters such as P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and multidrug resistance-associated proteins (MRPs) in intestinal absorption of methotrexate was examined in rats. In everted intestine, the mucosal efflux of methotrexate after application to serosal side was higher in jejunum than ileum, and the efflux in jejunum was suppressed by pantoprazole, a BCRP inhibitor, and probenecid, an MRP inhibitor, but not by verapamil, a P-gp inhibitor. The mucosal methotrexate efflux in ileum was suppressed by pantoprazole, but not by other inhibitors. On the other hand, the serosal efflux of methotrexate after application to mucosal side was greater in ileum than jejunum, and was suppressed by probenecid. In in-vivo rat studies, the intestinal absorption of methotrexate was significantly higher when methotrexate was administered to ileum than jejunum. Pantoprazole increased methotrexate absorption from jejunum and ileum. Probenecid increased the absorption of methotrexate from jejunum but decreased the absorption from ileum, as evaluated by peak plasma methotrexate levels. In conclusion, BCRP and MRPs are involved in the regional difference in absorption of methotrexate along the intestine, depending on their expression sites. SN - 0022-3573 UR - https://www.unboundmedicine.com/medline/citation/17883898/Role_of_intestinal_efflux_transporters_in_the_intestinal_absorption_of_methotrexate_in_rats_ L2 - https://doi.org/10.1211/jpp.59.9.0011 DB - PRIME DP - Unbound Medicine ER -