title: Improvement in the bioavailability of poorly absorbed glycyrrhizin via various non-vascular administration routes in rats.
abstract: The purpose of this study was to examine the improvement of the bioavailability of glycyrrhizin (GL) via extra-vascular, i.e. oral, rectal, and nasal routes with or without the aid of an absorption enhancer in place of the vascular intravenous route in rats. Pharmacokinetic behavior following administration via vascular routes, i.e. the intravenous and portal-venous routes was examined in rats. The area under the plasma concentration-time curve (AUC) after administration of GL via the portal vein was decreased slightly, suggesting that the first elimination of GL in the liver may be one of the factors contributing to the low bioavailability after administration via the oral route. When GL was administered orally as a solution (30 mg/kg), the plasma concentration of GL was extremely low. However, after rectal or nasal administration of GL solution (30 mg/kg) with or without sodium caprate, the mean AUC value was remarkably increased compared with oral administration. In particular, the absolute bioavailability of GL after nasal administration was estimated to be approximately 20%, which was approximately 80-fold greater compared with after oral administration despite of the absence of an enhancer. Furthermore, the fatty acids co-administered orally with GL produced an increase in GL absorption in the following order: sodium caprate>sodiumlaurate>sodiumcaprylate>sodium oleate. These results indicate that the rectum and nasal cavity are useful administration routes for systemic delivery of GL. It was also found that the fatty acids were enhancers for the absorption of GL.
authors.affiliation: Pharmaceutical Research Laboratory, Research and Development Division, Grelan Pharmaceutical Co. Ltd., Sakaecho-3-4-3, Hamura, Tokyo 205-0002, Japan. sasaki-k@grelan.co.jp
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sasaki
authors.forename: Shingo
authors.initials: S
authors.lastname: Yonebayashi
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Yoshida
authors.forename: Kenji
authors.initials: K
authors.lastname: Shimizu
authors.forename: Tomaji
authors.initials: T
authors.lastname: Aotsuka
authors.forename: Kozo
authors.initials: K
authors.lastname: Takayama
mesh_terms: D000042:Absorption; D000277:Adjuvants, Pharmaceutic / Q000737:chemistry*; D000281:Administration, Intranasal; D000284:Administration, Oral; D000285:Administration, Rectal; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D005227:Fatty Acids / Q000737:chemistry*; D019695:Glycyrrhizic Acid / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D008297:Male; D051381:Rats
chemical_list: D000277:Adjuvants, Pharmaceutic; D005227:Fatty Acids; D019695:Glycyrrhizic Acid