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In vitro and in vivo evaluation of the enhancing activity of glycyrrhizin on the intestinal absorption of drugs.
Pharm Res. 1999 Jan; 16(1):80-6.PR

Abstract

PURPOSE

The enhancing activity of dipotassium glycyrrhizinate (Grz) on the intestinal absorption of drugs has been demonstrated in an in vitro study using Caco-2 cell monolayers and in an in vivo absorption study in rats.

METHODS

The hydrolysis of Grz by luminal content and mucosa of the rat colon was investigated. The absorption-enhancing activity of Grz and its hydrolysates was estimated by changes in transepithelial electrical resistance (TEER) and the permeation of sodium fluorescein (Flu-Na) in Caco-2 cell monolayers. It was further evaluated through the absorption of salmon calcitonin (sCT) in the rat colon.

RESULTS

Grz was not hydrolyzed to glycyrrhetinylmonoglucuronide (GrMG) and glycyrrhetinic acid (GA) by colonic mucosa, but, rather by the beta-glucuronidase in colonic flora. The hydrolysis of Grz to GrMG was extremely slow and the GrMG produced was rapidly regenerated to GA. Grz and GrMG had no effect on TEER nor on the permeability of Flu-Na across Caco-2 cell monolayers. On the other hand, GA decreased TEER and increased the permeability of Flu-Na in a dose-dependent manner. However, Grz and GrMG enhanced the plasma calcium-lowering effect of sCT after administration in the rat colon. The coadministration of sCT and GA in the rat colon induced the strongest plasma calcium-lowering effect and the highest plasma concentration of sCT.

CONCLUSIONS

The in vivo enhancing-activity of Grz in the absorption of drugs is dependent on GA, a hydrolysis product of Grz resulting from the action of beta-glucuronidase in intestinal flora.

Authors+Show Affiliations

Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kumamoto University, Japan. iteruko@gpo.kumamoto-u.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

9950283

Citation

Imai, T, et al. "In Vitro and in Vivo Evaluation of the Enhancing Activity of Glycyrrhizin On the Intestinal Absorption of Drugs." Pharmaceutical Research, vol. 16, no. 1, 1999, pp. 80-6.
Imai T, Sakai M, Ohtake H, et al. In vitro and in vivo evaluation of the enhancing activity of glycyrrhizin on the intestinal absorption of drugs. Pharm Res. 1999;16(1):80-6.
Imai, T., Sakai, M., Ohtake, H., Azuma, H., & Otagiri, M. (1999). In vitro and in vivo evaluation of the enhancing activity of glycyrrhizin on the intestinal absorption of drugs. Pharmaceutical Research, 16(1), 80-6.
Imai T, et al. In Vitro and in Vivo Evaluation of the Enhancing Activity of Glycyrrhizin On the Intestinal Absorption of Drugs. Pharm Res. 1999;16(1):80-6. PubMed PMID: 9950283.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vitro and in vivo evaluation of the enhancing activity of glycyrrhizin on the intestinal absorption of drugs. AU - Imai,T, AU - Sakai,M, AU - Ohtake,H, AU - Azuma,H, AU - Otagiri,M, PY - 1999/2/9/pubmed PY - 1999/2/9/medline PY - 1999/2/9/entrez SP - 80 EP - 6 JF - Pharmaceutical research JO - Pharm Res VL - 16 IS - 1 N2 - PURPOSE: The enhancing activity of dipotassium glycyrrhizinate (Grz) on the intestinal absorption of drugs has been demonstrated in an in vitro study using Caco-2 cell monolayers and in an in vivo absorption study in rats. METHODS: The hydrolysis of Grz by luminal content and mucosa of the rat colon was investigated. The absorption-enhancing activity of Grz and its hydrolysates was estimated by changes in transepithelial electrical resistance (TEER) and the permeation of sodium fluorescein (Flu-Na) in Caco-2 cell monolayers. It was further evaluated through the absorption of salmon calcitonin (sCT) in the rat colon. RESULTS: Grz was not hydrolyzed to glycyrrhetinylmonoglucuronide (GrMG) and glycyrrhetinic acid (GA) by colonic mucosa, but, rather by the beta-glucuronidase in colonic flora. The hydrolysis of Grz to GrMG was extremely slow and the GrMG produced was rapidly regenerated to GA. Grz and GrMG had no effect on TEER nor on the permeability of Flu-Na across Caco-2 cell monolayers. On the other hand, GA decreased TEER and increased the permeability of Flu-Na in a dose-dependent manner. However, Grz and GrMG enhanced the plasma calcium-lowering effect of sCT after administration in the rat colon. The coadministration of sCT and GA in the rat colon induced the strongest plasma calcium-lowering effect and the highest plasma concentration of sCT. CONCLUSIONS: The in vivo enhancing-activity of Grz in the absorption of drugs is dependent on GA, a hydrolysis product of Grz resulting from the action of beta-glucuronidase in intestinal flora. SN - 0724-8741 UR - https://www.unboundmedicine.com/medline/citation/9950283/In_vitro_and_in_vivo_evaluation_of_the_enhancing_activity_of_glycyrrhizin_on_the_intestinal_absorption_of_drugs_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=9950283.ui DB - PRIME DP - Unbound Medicine ER -