title: Physiologically Based Pharmacokinetic and Absorption Modeling for Osmotic Pump Products.
abstract: Physiologically based pharmacokinetic (PBPK) and absorption modeling approaches were employed for oral extended-release (ER) drug products based on an osmotic drug delivery system (osmotic pumps). The purpose was to systemically evaluate the in vivo relevance of in vitro dissolution for this type of formulation. As expected, in vitro dissolution appeared to be generally predictive of in vivo PK profiles, because of the unique feature of this delivery system that the in vitro and in vivo release of osmotic pump drug products is less susceptible to surrounding environment in the gastrointestinal (GI) tract such as pH, hydrodynamic, and food effects. The present study considered BCS (Biopharmaceutics Classification System) class 1, 2, and 3 drug products with half-lives ranging from 2 to greater than 24 h. In some cases, the colonic absorption models needed to be adjusted to account for absorption in the colon. Cmax(maximum plasma concentration) and AUCt (area under the concentration curve) of the studied drug products were sensitive to changes in colon permeability and segmental GI transit times in a drug product-dependent manner. While improvement of the methodology is still warranted for more precise prediction (e.g., colonic absorption and dynamic movement in the GI tract), the results from the present study further emphasized the advantage of using PBPK modeling in addressing product-specific questions arising from regulatory review and drug development.
authors.affiliation: Division of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, US Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Zhanglin
authors.initials: Z
authors.lastname: Ni
authors.affiliation: Division of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, US Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Arjang
authors.initials: A
authors.lastname: Talattof
authors.affiliation: Division of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, US Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Jianghong
authors.initials: J
authors.lastname: Fan
authors.affiliation: Division of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, US Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Tsakalozou
authors.affiliation: Division of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, US Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Satish
authors.initials: S
authors.lastname: Sharan
authors.affiliation: Division of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, US Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Dajun
authors.initials: D
authors.lastname: Sun
authors.affiliation: Division of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, US Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Wen
authors.affiliation: Division of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, US Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Division of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, US Food and Drug Administration, Silver Spring, Maryland, USA. Xinyuan.Zhang@fda.hhs.gov.|, 10903 New Hampshire Ave., Bldg. 75, Room 4690, Silver Spring, Maryland, 20993, USA. Xinyuan.Zhang@fda.hhs.gov.
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Zhang
mesh_terms: D019540:Area Under Curve; D003692:Delayed-Action Preparations; D018565:Food-Drug Interactions; D041981:Gastrointestinal Tract / Q000378:metabolism; D008954:Models, Biological; D009995:Osmosis; D010599:Pharmacokinetics
chemical_list: D003692:Delayed-Action Preparations
keywords: Biopharmaceutics Classification System; osmotic pumps; physiologically based pharmacokinetic (PBPK) and absorption modeling