title: Application of physiologically based pharmacokinetic modeling in the prediction of pharmacokinetics of bicyclol controlled-release formulation in human.
abstract: Physiologically based pharmacokinetic (PBPK) modeling can assist in formulation development. Bicyclol is a novel anti-hepatitis drug. A bilayer osmotic pump table of bicyclol is being developed. PBPK models for bicyclol immediate-release (IR) and controlled-release (CR) tablets in beagle dog, as well as PBPK model for IR tablets in human were constructed. These models incorporated physicochemical properties and in vitro preclinical data. Parameter sensitivity analysis was performed for the effects of solubility and dissolution on pharmacokinetic (PK) parameters. Models were refined by comparing simulated results to experimental measurements. Furthermore, the clinical PK for bicyclol CR tablets was predicted using the in vivo dissolution profile by deconvolution of the mean PK profile of CR tablets in dogs. In summary, the present study described a strategy employing PBPK models to evaluate the effects of formulation factors on PK profiles and predict the performance of bicyclol CR tablets in human.
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Institute of Materia Medica, Chinese Academy of Medical Sciences & Perking Union Medical College, Beijing 100050, PR China.
authors.forename: Baolian
authors.initials: B
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Institute of Materia Medica, Chinese Academy of Medical Sciences & Perking Union Medical College, Beijing 100050, PR China.
authors.forename: Zhihao
authors.initials: Z
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Institute of Materia Medica, Chinese Academy of Medical Sciences & Perking Union Medical College, Beijing 100050, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Institute of Materia Medica, Chinese Academy of Medical Sciences & Perking Union Medical College, Beijing 100050, PR China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Institute of Materia Medica, Chinese Academy of Medical Sciences & Perking Union Medical College, Beijing 100050, PR China.
authors.forename: Jinping
authors.initials: J
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Institute of Materia Medica, Chinese Academy of Medical Sciences & Perking Union Medical College, Beijing 100050, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Institute of Materia Medica, Chinese Academy of Medical Sciences & Perking Union Medical College, Beijing 100050, PR China. Electronic address: shengli@imm.ac.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Sheng
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Institute of Materia Medica, Chinese Academy of Medical Sciences & Perking Union Medical College, Beijing 100050, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D001713:Biphenyl Compounds / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations; D004285:Dogs; D006801:Humans; D008954:Models, Biological
chemical_list: D001713:Biphenyl Compounds; D003692:Delayed-Action Preparations; C477843:bicyclol
keywords: Bicyclol; Dog; Human; PBPK; Pharmacokinetic