title: Cationic analog of deoxycholate as an oral delivery carrier for ceftriaxone.
abstract: A great number of currently available drugs and those being developed that fall under the class III of the BCS (biopharmaceutical classification system) possess high therapeutic potential but cannot be delivered by peroral absorption. In this study, we synthesized a cationic analog of deoxycholic acid and evaluated its efficacy as a potential oral drug carrier for anionic BCS class III drugs using ceftriaxone as a model drug. Cationic deoxycholylethylamine (DCEA), one of cationic analogs of deoxycholic acid, was synthesized and made into physical complexes at varied molar ratios with an anionic ceftriaxone. These drug complexes were formulated with propylene glycol and their oral bioavailabilities were evaluated. The results of the partition coefficient study revealed a highly water soluble ceftriaxone that became more hydrophobic as the molar ratio of the carrier in the complex increased. When the ceftriaxone/DCEA formulation was administered into a nonclosed segment of duodenum of rats, C(max) (the maximum drug concentration in plasma) and AUC (area under the curve) were significantly increased and its bioavailability was increased up to 70%. Therefore, the new cationic carriers proposed in this study could improve the absorption of BCS class III drugs in the intestine with maintaining their full biological activity.
authors.affiliation: Department of Materials Science and Engineering, Center for Cell and Macromolecular Therapy, Gwangju Institute of Science and Technology, 1 Oryong-dong Buk-gu Gwangju 500-712, Korea.
authors.forename: Seulki
authors.initials: S
authors.lastname: Lee
authors.forename: Sang Kyoon
authors.initials: SK
authors.lastname: Kim
authors.forename: Dong Yun
authors.initials: DY
authors.lastname: Lee
authors.forename: Kyeongsoon
authors.initials: K
authors.lastname: Park
authors.forename: Tadiparthi Suresh
authors.initials: TS
authors.lastname: Kumar
authors.forename: Su Young
authors.initials: SY
authors.lastname: Chae
authors.forename: Youngro
authors.initials: Y
authors.lastname: Byun
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D001702:Biopharmaceutics; D002412:Cations; D002443:Ceftriaxone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D003840:Deoxycholic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D004337:Drug Carriers; D004386:Duodenum / Q000378:metabolism; D006207:Half-Life; D007408:Intestinal Absorption; D008297:Male; D008657:Metabolic Clearance Rate; D019946:Propylene Glycol / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000900:Anti-Bacterial Agents; D002412:Cations; D004337:Drug Carriers; C507172:N-deoxychoylethylenediamine; D003840:Deoxycholic Acid; D019946:Propylene Glycol; D002443:Ceftriaxone