IMI – oral biopharmaceutics tools project – evaluation of bottom-up PBPK prediction success part 1: Characterisation of the OrBiTo database of compounds

Autor: Franziska Graf, Wolfgang Mück, Dominique Swerts, Kerstin J. Frank, Dorina van der Mey, Joanne Bennett, Marta Venczel, Thomas Müller, Uwe Muenster, Hans Lennernäs, Florent Mazuir, Jan Bevernage, Mei Wong, Mark McAllister, Stéphane Beilles, Loic Laplanche, Alison Margolskee, Stefania Beato, Lieve Adriaenssen, Loeckie de Zwart, Jonas Angstenberger, Xavier Pepin, Anh-Thu Nguyen-Trung, Alexander Marker, Amin Rostami-Hodjegan, P. Zane, Céline Ollier, An Van Den Bergh, Adam S. Darwich, Shriram M. Pathak, Dónal Murphy, Markus Kolhmann, Pankaj Daga, Susanne Greschat-Schade, Michael B. Bolger, Achiel Van Peer, Christer Tannergren, Priscilla Brun, Mohammed Yasin, Bertil Abrahamsson, Sara Carlert, Richard Lloyd, Christophe Tistaert, Leon Aarons, Petra Loos, Xavier Boulenc, Pascale Vicat
Rok vydání: 2017
Předmět:
Zdroj: Margolskee, A, Darwich, A, Pepin, X, Pathak, S M, Bolger et al, M B, Aarons, L, Rostami-Hochaghan, A, Angstenberger, J, Graf, F, Laplanche, L, Muller, T, Carlert, S, Daga, P, Murphy, D, Tannergren, C, Yasin, M, Greschat-Schade, S, Muck, W, Muenster, U, van der Mey, D, Frank, K, Lloyd, R, Adriaenssen, L, Bevernage, J, De Zwart, L, Swerts, D, Tistaert, C, Van Den Bergh, A, Van Peer, A, Beato, S, Nguyen-Trung, A-T, Bennett, J, McAllister, M, Wong, M, Zane, P, Ollier, C, Vicat, P, Kolhmann, M, Marker, A, Brun, P, Mazuir, F, Beilles, S, Venczel, M, Boulenc, X, Loos, P, Lennernas, H & Abrahamsson, B 2016, ' IMI – oral biopharmaceutics tools project – evaluation of bottom-up PBPK prediction success part 1: Characterisation of the OrBiTo database of compounds ', European Journal of Pharmaceutical Sciences . https://doi.org/10.1016/j.ejps.2016.09.027
ISSN: 0928-0987
DOI: 10.1016/j.ejps.2016.09.027
Popis: 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 16.9 L/h (interquartile range: 11.6–43.6 L/h; n = 23), volume of distribution was 80.8 L (54.5–239 L; 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.
Databáze: OpenAIRE
Externí odkaz: