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Improvement of intestinal absorption of P-glycoprotein substrate by D-tartaric acid.
Drug Metab Pharmacokinet. 2006 Oct; 21(5):424-8.DM

Abstract

The purpose of the present experiment was to examine the effects of D-tartaric acid (TA) on intestinal drug absorption under both in situ and in vitro experimental conditions. In the in vitro diffusion chamber experiments, TA (10 mM) added to the mucosal side of rat colon significantly decreased rhodamine123 (Rho 123) transport from the serosal to mucosal side. Since TA has been shown to change the integrity of the epithelial tight junctions in rat colon at low pH conditions, resulting in improved paracellular drug transport, the effect of TA on membrane resistance was examined at pH 7.4 in the present study. It was found that membrane resistance, an indicator of paracellular integrity, did not change at pH 7.4. In the in situ loop method, TA (20 mM) increased the absorption of Rho123 in both ileum and colon but not in jejunum. TA (20 mM) also increased the absorption of daunorubicin in the ileum, but TA (20 mM) did not change the expression level of P-glycoprotein (P-gp). TA (20 mM) significantly inhibited excretion of i.v.-administered Rho123 and daunorubicin into the ileal lumen. In conclusion, for the first time we demonstrated that TA increases the intestinal absorption of P-gp substrates Rho123 and daunorubicin, possibly by modulating the P-gp function without changing the expression level of P-gp in the rat intestine.

Authors+Show Affiliations

Department of Drug Absorption and Pharmacokinetics, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji, Tokyo, Japan. aiai_dada@hotmail.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17072096

Citation

Iida, Aiko, et al. "Improvement of Intestinal Absorption of P-glycoprotein Substrate By D-tartaric Acid." Drug Metabolism and Pharmacokinetics, vol. 21, no. 5, 2006, pp. 424-8.
Iida A, Tomita M, Idota Y, et al. Improvement of intestinal absorption of P-glycoprotein substrate by D-tartaric acid. Drug Metab Pharmacokinet. 2006;21(5):424-8.
Iida, A., Tomita, M., Idota, Y., Takizawa, Y., & Hayashi, M. (2006). Improvement of intestinal absorption of P-glycoprotein substrate by D-tartaric acid. Drug Metabolism and Pharmacokinetics, 21(5), 424-8.
Iida A, et al. Improvement of Intestinal Absorption of P-glycoprotein Substrate By D-tartaric Acid. Drug Metab Pharmacokinet. 2006;21(5):424-8. PubMed PMID: 17072096.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Improvement of intestinal absorption of P-glycoprotein substrate by D-tartaric acid. AU - Iida,Aiko, AU - Tomita,Mikio, AU - Idota,Yoko, AU - Takizawa,Yusuke, AU - Hayashi,Masahiro, PY - 2006/10/31/pubmed PY - 2007/1/17/medline PY - 2006/10/31/entrez SP - 424 EP - 8 JF - Drug metabolism and pharmacokinetics JO - Drug Metab Pharmacokinet VL - 21 IS - 5 N2 - The purpose of the present experiment was to examine the effects of D-tartaric acid (TA) on intestinal drug absorption under both in situ and in vitro experimental conditions. In the in vitro diffusion chamber experiments, TA (10 mM) added to the mucosal side of rat colon significantly decreased rhodamine123 (Rho 123) transport from the serosal to mucosal side. Since TA has been shown to change the integrity of the epithelial tight junctions in rat colon at low pH conditions, resulting in improved paracellular drug transport, the effect of TA on membrane resistance was examined at pH 7.4 in the present study. It was found that membrane resistance, an indicator of paracellular integrity, did not change at pH 7.4. In the in situ loop method, TA (20 mM) increased the absorption of Rho123 in both ileum and colon but not in jejunum. TA (20 mM) also increased the absorption of daunorubicin in the ileum, but TA (20 mM) did not change the expression level of P-glycoprotein (P-gp). TA (20 mM) significantly inhibited excretion of i.v.-administered Rho123 and daunorubicin into the ileal lumen. In conclusion, for the first time we demonstrated that TA increases the intestinal absorption of P-gp substrates Rho123 and daunorubicin, possibly by modulating the P-gp function without changing the expression level of P-gp in the rat intestine. SN - 1347-4367 UR - https://www.unboundmedicine.com/medline/citation/17072096/Improvement_of_intestinal_absorption_of_P_glycoprotein_substrate_by_D_tartaric_acid_ L2 - http://joi.jlc.jst.go.jp/JST.JSTAGE/dmpk/21.424?from=PubMed DB - PRIME DP - Unbound Medicine ER -