Enhanced oral absorption of ibandronate via complex formation with bile acid derivative.
J Pharm Sci
; 102(2): 341-6, 2013 Feb.
Article
em En
| MEDLINE
| ID: mdl-23233267
ABSTRACT
Bisphosphonates are recommended for the treatment of postmenopausal osteoporosis, Paget's disease, bone metastasis, and multiple myeloma. However, the efficacy of oral preparations is limited because of their low bioavailabilities and adverse effects from the gastrointestinal tract. This study was conducted to investigate whether N(α)-deoxycholyl-L-lysyl-methylester (DCK), an absorption enhancer derived from deoxycholic acid, can increase the oral bioavailability of ibandronate. We prepared a physical complex of ibandronate with DCK, and evaluated its permeability across a parallel artificial membrane. Furthermore, pharmacokinetic profile and oral absorption of the optimized formulation were also studied in rats. DCK enhanced the apparent membrane permeability of ibandronate by 14.4-fold in a parallel artificial membrane permeability assay model, compared with when ibandronate was applied alone. When ibandronate-DCK complex was intrajejunally administered to rats, it resulted in a 2.8- and 4.3-fold increase in maximum plasma concentration and area under the concentration-time curve from time zero to the last measurable time point, respectively. These results demonstrate that the ibandronate-DCK formulation can improve the oral absorption of ibandronate, allowing less frequent dosing to avoid side effects as well to enhance patient compliance.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácidos e Sais Biliares
/
Portadores de Fármacos
/
Química Farmacêutica
/
Difosfonatos
/
Absorção Intestinal
Limite:
Animals
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article