title: Quantitative analysis of lab-to-lab variability in Caco-2 permeability assays.
abstract: In this study, Caco-2 permeability results from different laboratories were compared. Six different sets of apparent permeability coefficient (Papp) values reported in the literature were compared to experimental Pappobtained in our laboratory. The differences were assessed by determining the root mean square error (RMSE) values between the datasets, which reached levels as high as 0.581 for the training set compounds, i.e. ten compounds with known effective human permeability (Peff). The consequences of these differences in Pappfor prediction of oral drug absorption were demonstrated by introducing the Pappinto the absorption and pharmacokinetics simulation software application GastroPlus™ for prediction of the fraction absorbed (Fa) in humans using calibrated "user-defined permeability models". The RMSE were calculated to assess the differences between the simulated Faand experimental values reported in the literature. The RMSE for Fasimulated with the permeability model calibrated using experimental Pappfrom our laboratory was 0.128. When the calibration was performed using Pappfrom literature datasets, the RMSE values for Fawere higher in all cases except one. This study shows quantitative lab-to-lab variability of Caco-2 permeability results and the potential consequences this can have in the use of these results for predicting intestinal absorption of drugs.
authors.affiliation: School of Pharmacy, University of Nottingham, Nottingham, UK.
authors.forename: Jong Bong
authors.initials: JB
authors.lastname: Lee
authors.affiliation: School of Pharmacy, University of Nottingham, Nottingham, UK; College of Pharmacy, University of Anbar, Anbar, Iraq.
authors.forename: Atheer
authors.initials: A
authors.lastname: Zgair
authors.affiliation: School of Pharmacy, University of Nottingham, Nottingham, UK.
authors.forename: Dhiaa A
authors.initials: DA
authors.lastname: Taha
authors.affiliation: Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zang
authors.affiliation: Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
authors.forename: Leonid
authors.initials: L
authors.lastname: Kagan
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.
authors.forename: Tae Hwan
authors.initials: TH
authors.lastname: Kim
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.
authors.forename: Min Gi
authors.initials: MG
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Hwi-Yeol
authors.initials: HY
authors.lastname: Yun
authors.affiliation: School of Pharmacy, University of Nottingham, Nottingham, UK.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Fischer
authors.affiliation: School of Pharmacy, University of Nottingham, Nottingham, UK. Electronic address: pavel.gershkovich@nottingham.ac.uk.
authors.forename: Pavel
authors.initials: P
authors.lastname: Gershkovich
mesh_terms: D000327:Adsorption; D018938:Caco-2 Cells / Q000378:metabolism*; D002138:Calibration; D002463:Cell Membrane Permeability; D003198:Computer Simulation; D016208:Databases, Factual; D006801:Humans; D007408:Intestinal Absorption; D004364:Pharmaceutical Preparations / Q000378:metabolism; D011237:Predictive Value of Tests; D015203:Reproducibility of Results
chemical_list: D004364:Pharmaceutical Preparations
keywords: Caco-2 permeability assay; Drug permeability; GastroPlus™; Lab-to-lab variability; Prediction of oral absorption