title: Comparative efficacy and bioequivalence of novel h1-antihistamine bepotastine salts (nicotinate and salicylate).
abstract: Bepotastine salts (nicotinate and salicylate) were investigated for their physicochemical properties to develop novel salt forms of bepotastine, bioequivalent to the bepotastine besilate-loaded tablet (Talion). These bepotastine salts of either nicotinate- or salicylate-loaded tablets were prepared by conventional wet granulation method, and dissolution profiles and pharmacokinetics in beagle dogs were compared to those of Talion. A novel bepotastine nicotinate has a higher solubility at varying pH levels (1.2, 4, or 6.8) than salicylate-loaded or besilate-loaded salt. In addition, those bepostastine salt forms (nicotinate and salicylate) are stable in heat, light, and water. Further, the novel nicotinate- and salicylate-loaded tablets showed similar dissolution rates to Talion in several selected dissolution media and were bioequivalent to Talion in beagle dogs in terms of area under the concentration-time curve (AUC) and maximum observed concentration (Cmax). A pharmacokinetic study performed in beagle dogs demonstrated that test and reference products were found to be bioequivalent in terms of safety, efficacy, and pharmacokinetic properties. These results suggest that bepostastine nicotinate and salicylate formulations are considered applicable candidates and are well tolerated versus the conventional bepostastine besilate formulation.
authors.affiliation: a Division of Pharmaceutics and Toxicology , College of Pharmacy, Sungkyunkwan University, Cheoncheon-Dong 300 , Changan-Ku, Gyeonggi-Do , Suwon , South Korea.
authors.forename: Duck Soo
authors.initials: DS
authors.lastname: Lim
authors.forename: Yoo Seok
authors.initials: YS
authors.lastname: Youn
authors.forename: Seung Jun
authors.initials: SJ
authors.lastname: Kwack
authors.forename: Hyo Min
authors.initials: HM
authors.lastname: Kwak
authors.forename: Seong Kwang
authors.initials: SK
authors.lastname: Lim
authors.forename: Ji Yun
authors.initials: JY
authors.lastname: Kim
authors.forename: Yoon Mi
authors.initials: YM
authors.lastname: Um
authors.forename: Jung Dae
authors.initials: JD
authors.lastname: Lee
authors.forename: Ji Hyeon
authors.initials: JH
authors.lastname: Hyeon
authors.forename: Yeon Joo
authors.initials: YJ
authors.lastname: Kim
authors.forename: Hyung Sik
authors.initials: HS
authors.lastname: Kim
authors.forename: Byung-Mu
authors.initials: BM
authors.lastname: Lee
mesh_terms: D000818:Animals; D055598:Chemical Phenomena; D002853:Chromatography, Liquid; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D006633:Histamine Antagonists / Q000493:pharmacokinetics*; D006863:Hydrogen-Ion Concentration; D008297:Male; D009525:Niacin / Q000493:pharmacokinetics*; D010880:Piperidines / Q000493:pharmacokinetics*; D011725:Pyridines / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012459:Salicylates / Q000493:pharmacokinetics*; D013607:Tablets / Q000737:chemistry; D053719:Tandem Mass Spectrometry; D013810:Therapeutic Equivalency
chemical_list: D006633:Histamine Antagonists; D010880:Piperidines; D011725:Pyridines; D012459:Salicylates; D013607:Tablets; D009525:Niacin; C108476:bepotastine