title: Oral delivery of ionic complex of ceftriaxone with bile acid derivative in non-human primates.
abstract: OBJECTIVE
  Since the absorption of ceftriaxone (CTO) in the intestine is restricted by its natural physiological characteristics, we developed a series of small synthetic compounds derived from bile acids to promote the absorption of CTO in the gastrointestinal tract.
  
  
  METHODS
  Several bile acid derivatives were screened by measuring water solubility and partition coefficient of their complexes with CTO. The pharmacokinetic parameters of the selected CTO/HDCK ionic complex in monkeys were evaluated. The absorption pathway of CTO/HDCK complex was evaluated using Caco-2 cells and MDCK cells transfected with ASBT gene.
  
  
  RESULTS
  HDCK enhanced the apparent membrane permeability of CTO 5.8-fold in the parallel artificial membrane permeability assay model. CTO/HDCK complex permeated Caco-2 cell via transcellular pathway, and interaction of the HDCK complex with ASBT was important to enhance uptake. When CTO/HDCK (equivalent to 50 mg/kg of ceftriaxone) formulated with lactose, poloxamer 407 and Labrasol was orally administered to monkeys, its maximum plasma concentration was 19.5 ± 1.8 μg/ml and oral bioavailability 28.5 ± 3.1%.
  
  
  CONCLUSIONS
  The CTO/HDCK formulation could enhance oral bioavailability of CTO in non-human primates. This oral formulation could be an alternative to injectable CTO with enhanced clinical effects.
authors.affiliation: Department of Polymer Science and Engineering, Sungkyunkwan University, Suwon, 440-746, South Korea.
authors.forename: Ok-Cheol
authors.initials: OC
authors.lastname: Jeon
authors.forename: Seung Rim
authors.initials: SR
authors.lastname: Hwang
authors.forename: Taslim A
authors.initials: TA
authors.lastname: Al-Hilal
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Park
authors.forename: Hyun Tae
authors.initials: HT
authors.lastname: Moon
authors.forename: Seulki
authors.initials: S
authors.lastname: Lee
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Park
authors.forename: Youngro
authors.initials: Y
authors.lastname: Byun
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D001647:Bile Acids and Salts / Q000737:chemistry*; D018938:Caco-2 Cells; D002443:Ceftriaxone / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D002460:Cell Line; D004285:Dogs; D004337:Drug Carriers / Q000737:chemistry*; D000882:Haplorhini; D006801:Humans; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics / Q000378:metabolism; D010539:Permeability; D012995:Solubility; D027981:Symporters / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D000900:Anti-Bacterial Agents; D001647:Bile Acids and Salts; D004337:Drug Carriers; D029363:Organic Anion Transporters, Sodium-Dependent; D027981:Symporters; C071908:sodium-bile acid cotransporter; D002443:Ceftriaxone