Abstract
Purpose: 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.
Original language | English (US) |
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Pages (from-to) | 959-967 |
Number of pages | 9 |
Journal | Pharmaceutical Research |
Volume | 30 |
Issue number | 4 |
DOIs | |
State | Published - Apr 2013 |
Externally published | Yes |
Keywords
- ceftriaxone
- deoxycholic acid
- enhancer
- ionic complex
- oral delivery
ASJC Scopus subject areas
- Biotechnology
- Molecular Medicine
- Pharmacology
- Pharmaceutical Science
- Organic Chemistry
- Pharmacology (medical)