title: Enhanced oral absorption of ibandronate via complex formation with bile acid derivative.
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.
authors.affiliation: Amorepacific Corporation R&D Center, Giheung-gu, Yongin-si, Gyeonggi-do 446-729, South Korea.
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Park
authors.forename: Seung Rim
authors.initials: SR
authors.lastname: Hwang
authors.forename: Ok-Cheol
authors.initials: OC
authors.lastname: Jeon
authors.forename: Hyun Tae
authors.initials: HT
authors.lastname: Moon
authors.forename: Youngro
authors.initials: Y
authors.lastname: Byun
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001647:Bile Acids and Salts / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004164:Diphosphonates / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D000077557:Ibandronic Acid; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D001647:Bile Acids and Salts; D004164:Diphosphonates; D004337:Drug Carriers; D000077557:Ibandronic Acid