TY - JOUR T1 - IMI - oral biopharmaceutics tools project - evaluation of bottom-up PBPK prediction success part 1: Characterisation of the OrBiTo database of compounds. AU - Margolskee,Alison, AU - Darwich,Adam S, AU - Pepin,Xavier, AU - Pathak,Shriram M, AU - Bolger,Michael B, AU - Aarons,Leon, AU - Rostami-Hodjegan,Amin, AU - Angstenberger,Jonas, AU - Graf,Franziska, AU - Laplanche,Loic, AU - Müller,Thomas, AU - Carlert,Sara, AU - Daga,Pankaj, AU - Murphy,Dónal, AU - Tannergren,Christer, AU - Yasin,Mohammed, AU - Greschat-Schade,Susanne, AU - Mück,Wolfgang, AU - Muenster,Uwe, AU - van der Mey,Dorina, AU - Frank,Kerstin Julia, AU - Lloyd,Richard, AU - Adriaenssen,Lieve, AU - Bevernage,Jan, AU - De Zwart,Loeckie, AU - Swerts,Dominique, AU - Tistaert,Christophe, AU - Van Den Bergh,An, AU - Van Peer,Achiel, AU - Beato,Stefania, AU - Nguyen-Trung,Anh-Thu, AU - Bennett,Joanne, AU - McAllister,Mark, AU - Wong,Mei, AU - Zane,Patricia, AU - Ollier,Céline, AU - Vicat,Pascale, AU - Kolhmann,Markus, AU - Marker,Alexander, AU - Brun,Priscilla, AU - Mazuir,Florent, AU - Beilles,Stéphane, AU - Venczel,Marta, AU - Boulenc,Xavier, AU - Loos,Petra, AU - Lennernäs,Hans, AU - Abrahamsson,Bertil, Y1 - 2016/09/23/ PY - 2016/05/10/received PY - 2016/08/12/revised PY - 2016/09/17/accepted PY - 2016/9/28/pubmed PY - 2017/4/7/medline PY - 2016/9/28/entrez KW - Absorption KW - Biopharmaceutics KW - Drug database KW - Modelling and simulation (M&S) KW - Oral bioavailability (F(oral)) KW - Physiologically-based pharmacokinetics (PBPK) SP - 598 EP - 609 JF - European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences JO - Eur J Pharm Sci VL - 96 N2 - Predicting oral bioavailability (Foral) is of importance for estimating systemic exposure of orally administered drugs. Physiologically-based pharmacokinetic (PBPK) modelling and simulation have been applied extensively in biopharmaceutics recently. The Oral Biopharmaceutical Tools (OrBiTo) project (Innovative Medicines Initiative) aims to develop and improve upon biopharmaceutical tools, including PBPK absorption models. A large-scale evaluation of PBPK models may be considered the first step. Here we characterise the OrBiTo active pharmaceutical ingredient (API) database for use in a large-scale simulation study. The OrBiTo database comprised 83 APIs and 1475 study arms. The database displayed a median logP of 3.60 (2.40-4.58), human blood-to-plasma ratio of 0.62 (0.57-0.71), and fraction unbound in plasma of 0.05 (0.01-0.17). The database mainly consisted of basic compounds (48.19%) and Biopharmaceutics Classification System class II compounds (55.81%). Median human intravenous clearance was 16.9L/h (interquartile range: 11.6-43.6L/h; n=23), volume of distribution was 80.8L (54.5-239L; n=23). The majority of oral formulations were immediate release (IR: 87.6%). Human Foral displayed a median of 0.415 (0.203-0.724; n=22) for IR formulations. The OrBiTo database was found to be largely representative of previously published datasets. 43 of the APIs were found to satisfy the minimum inclusion criteria for the simulation exercise, and many of these have significant gaps of other key parameters, which could potentially impact the interpretability of the simulation outcome. However, the OrBiTo simulation exercise represents a unique opportunity to perform a large-scale evaluation of the PBPK approach to predicting oral biopharmaceutics. SN - 1879-0720 UR - https://www.unboundmedicine.com/medline/citation/27671970/IMI___oral_biopharmaceutics_tools_project___evaluation_of_bottom_up_PBPK_prediction_success_part_1:_Characterisation_of_the_OrBiTo_database_of_compounds_ DB - PRIME DP - Unbound Medicine ER -