PMID- 32805361
OWN - NLM
STAT- MEDLINE
DCOM- 20210707
LR  - 20210707
IS  - 1873-3441 (Electronic)
IS  - 0939-6411 (Linking)
VI  - 156
DP  - 2020 Nov
TI  - IMI - Oral biopharmaceutics tools project - Evaluation of bottom-up PBPK 
      prediction success part 4: Prediction accuracy and software comparisons with 
      improved data and modelling strategies.
PG  - 50-63
LID - S0939-6411(20)30241-1 [pii]
LID - 10.1016/j.ejpb.2020.08.006 [doi]
AB  - Oral drug absorption is a complex process depending on many factors, including 
      the physicochemical properties of the drug, formulation characteristics and their 
      interplay with gastrointestinal physiology and biology. Physiological-based 
      pharmacokinetic (PBPK) models integrate all available information on 
      gastro-intestinal system with drug and formulation data to predict oral drug 
      absorption. The latter together with in vitro-in vivo extrapolation and other 
      preclinical data on drug disposition can be used to predict plasma 
      concentration-time profiles in silico. Despite recent successes of PBPK in many 
      areas of drug development, an improvement in their utility for evaluating oral 
      absorption is much needed. Current status of predictive performance, within the 
      confinement of commonly available in vitro data on drugs and formulations 
      alongside systems information, were tested using 3 PBPK software packages (GI-Sim 
      (ver.4.1), Simcyp(R) Simulator (ver.15.0.86.0), and GastroPlus (ver.9.0.00xx)). 
      This was part of the Innovative Medicines Initiative (IMI) Oral Biopharmaceutics 
      Tools (OrBiTo) project. Fifty eight active pharmaceutical ingredients (APIs) were 
      qualified from the OrBiTo database to be part of the investigation based on a 
      priori set criteria on availability of minimum necessary information to allow 
      modelling exercise. The set entailed over 200 human clinical studies with over 
      700 study arms. These were simulated using input parameters which had been 
      harmonised by a panel of experts across different software packages prior to 
      conduct of any simulation. Overall prediction performance and software packages 
      comparison were evaluated based on performance indicators (Fold error (FE), 
      Average fold error (AFE) and absolute average fold error (AAFE)) of 
      pharmacokinetic (PK) parameters. On average, PK parameters (Area Under the 
      Concentration-time curve (AUC(0-tlast)), Maximal concentration (C(max)), 
      half-life (t(1/2))) were predicted with AFE values between 1.11 and 1.97. 
      Variability in FEs of these PK parameters was relatively high with AAFE values 
      ranging from 2.08 to 2.74. Around half of the simulations were within the 2-fold 
      error for AUC(0-tlast) and around 90% of the simulations were within 10-fold 
      error for AUC(0-tlast). Oral bioavailability (F(oral)) predictions, which were 
      limited to 19 APIs having intravenous (i.v.) human data, showed AFE and AAFE of 
      values 1.37 and 1.75 respectively. Across different APIs, AFE of AUC(0-tlast) 
      predictions were between 0.22 and 22.76 with 70% of the APIs showing an AFE > 1. 
      When compared across different formulations and routes of administration, 
      AUC(0-tlast) for oral controlled release and i.v. administration were better 
      predicted than that for oral immediate release formulations. Average predictive 
      performance did not clearly differ between software packages but some APIs showed 
      a high level of variability in predictive performance across different software 
      packages. This variability could be related to several factors such as compound 
      specific properties, the quality and availability of information, and errors in 
      scaling from in vitro and preclinical in vivo data to human in vivo behaviour 
      which will be explored further. Results were compared with previous similar 
      exercise when the input data selection was carried by the modeller rather than a 
      panel of experts on each in vitro test. Overall, average predictive performance 
      was increased as reflected in smaller AAFE value of 2.8 as compared to AAFE value 
      of 3.8 in case of previous exercise.
CI  - Copyright (c) 2020 Elsevier B.V. All rights reserved.
FAU - Ahmad, Amais
AU  - Ahmad A
AD  - University of Manchester, United Kingdom. Electronic address: 
      amais.ahmed@manchester.ac.uk.
FAU - Pepin, Xavier
AU  - Pepin X
AD  - AstraZeneca, United Kingdom.
FAU - Aarons, Leon
AU  - Aarons L
AD  - University of Manchester, United Kingdom.
FAU - Wang, Yuya
AU  - Wang Y
AD  - University of Manchester, United Kingdom.
FAU - Darwich, Adam S
AU  - Darwich AS
AD  - Royal Institute of Technology, Stockholm, Sweden.
FAU - Wood, J Matthew
AU  - Wood JM
AD  - AstraZeneca, United Kingdom.
FAU - Tannergren, Christer
AU  - Tannergren C
AD  - AstraZeneca, United Kingdom.
FAU - Karlsson, Eva
AU  - Karlsson E
AD  - AstraZeneca, United Kingdom.
FAU - Patterson, Claire
AU  - Patterson C
AD  - AstraZeneca, United Kingdom.
FAU - Thorn, Helena
AU  - Thorn H
AD  - AstraZeneca, United Kingdom.
FAU - Ruston, Linette
AU  - Ruston L
AD  - AstraZeneca, United Kingdom.
FAU - Mattinson, Alex
AU  - Mattinson A
AD  - AstraZeneca, United Kingdom.
FAU - Carlert, Sara
AU  - Carlert S
AD  - AstraZeneca, United Kingdom.
FAU - Berg, Staffan
AU  - Berg S
AD  - AstraZeneca, United Kingdom.
FAU - Murphy, Donal
AU  - Murphy D
AD  - AstraZeneca, United Kingdom.
FAU - Engman, Helena
AU  - Engman H
AD  - AstraZeneca, United Kingdom.
FAU - Laru, Johanna
AU  - Laru J
AD  - AstraZeneca, United Kingdom.
FAU - Barker, Richard
AU  - Barker R
AD  - AstraZeneca, United Kingdom.
FAU - Flanagan, Talia
AU  - Flanagan T
AD  - AstraZeneca, United Kingdom.
FAU - Abrahamsson, Bertil
AU  - Abrahamsson B
AD  - AstraZeneca, United Kingdom.
FAU - Budhdeo, Shanoo
AU  - Budhdeo S
AD  - AstraZeneca, United Kingdom.
FAU - Franek, Frans
AU  - Franek F
AD  - AstraZeneca, United Kingdom.
FAU - Moir, Andrea
AU  - Moir A
AD  - AstraZeneca, United Kingdom.
FAU - Hanisch, Gunilla
AU  - Hanisch G
AD  - AstraZeneca, United Kingdom.
FAU - Pathak, Shriram M
AU  - Pathak SM
AD  - Certara, Simcyp Division, United Kingdom.
FAU - Turner, David
AU  - Turner D
AD  - Certara, Simcyp Division, United Kingdom.
FAU - Jamei, Masoud
AU  - Jamei M
AD  - Certara, Simcyp Division, United Kingdom.
FAU - Brown, Jonathan
AU  - Brown J
AD  - Bristol-Myers Squibb, United Kingdom.
FAU - Good, David
AU  - Good D
AD  - Bristol-Myers Squibb, United Kingdom.
FAU - Vaidhyanathan, Shruthi
AU  - Vaidhyanathan S
AD  - Bristol-Myers Squibb, United Kingdom.
FAU - Jackson, Claire
AU  - Jackson C
AD  - Bristol-Myers Squibb, United Kingdom.
FAU - Nicolas, Olivier
AU  - Nicolas O
AD  - Sanofi, United States.
FAU - Beilles, Stephane
AU  - Beilles S
AD  - Sanofi, United States.
FAU - Nguefack, Jean-Flaubert
AU  - Nguefack JF
AD  - Sanofi, United States.
FAU - Louit, Guillaume
AU  - Louit G
AD  - Sanofi, United States.
FAU - Henrion, Louis
AU  - Henrion L
AD  - Sanofi, United States.
FAU - Ollier, Celine
AU  - Ollier C
AD  - Sanofi, United States.
FAU - Boulu, Laurent
AU  - Boulu L
AD  - Sanofi, United States.
FAU - Xu, Christine
AU  - Xu C
AD  - Sanofi, United States.
FAU - Heimbach, Tycho
AU  - Heimbach T
AD  - Novartis, United States.
FAU - Ren, Xiojun
AU  - Ren X
AD  - Novartis, United States.
FAU - Lin, Wen
AU  - Lin W
AD  - Novartis, United States.
FAU - Nguyen-Trung, Anh-Thu
AU  - Nguyen-Trung AT
AD  - Novartis, United States.
FAU - Zhang, Jin
AU  - Zhang J
AD  - Novartis, United States.
FAU - He, Handan
AU  - He H
AD  - Novartis, United States.
FAU - Wu, Fan
AU  - Wu F
AD  - Novartis, United States.
FAU - Bolger, Michael B
AU  - Bolger MB
AD  - Simulation Plus, Inc., United States.
FAU - Mullin, James M
AU  - Mullin JM
AD  - Simulation Plus, Inc., United States.
FAU - van Osdol, Bill
AU  - van Osdol B
AD  - Simulation Plus, Inc., United States.
FAU - Szeto, Ke
AU  - Szeto K
AD  - Simulation Plus, Inc., United States.
FAU - Korjamo, Timo
AU  - Korjamo T
AD  - Orion Pharma, Finland.
FAU - Pappinen, Sari
AU  - Pappinen S
AD  - Orion Pharma, Finland.
FAU - Tuunainen, Johanna
AU  - Tuunainen J
AD  - Orion Pharma, Finland.
FAU - Zhu, Wei
AU  - Zhu W
AD  - Merck Research Laboratories, Merck & Co., United States.
FAU - Xia, Binfeng
AU  - Xia B
AD  - Merck Research Laboratories, Merck & Co., United States.
FAU - Daublain, Pierre
AU  - Daublain P
AD  - Merck Research Laboratories, Merck & Co., United States.
FAU - Wong, Suet
AU  - Wong S
AD  - Pfizer, United States.
FAU - Varma, Manthena V S
AU  - Varma MVS
AD  - Pfizer, United States.
FAU - Modi, Sweta
AU  - Modi S
AD  - Pfizer, United States.
FAU - Schafer, Kerstin Julia
AU  - Schafer KJ
AD  - Boehringer-ingelheim, Germany.
FAU - Schmid, Kartrin
AU  - Schmid K
AD  - Boehringer-ingelheim, Germany.
FAU - Lloyd, Richard
AU  - Lloyd R
AD  - GlaxoSmithKline, United Kingdom.
FAU - Patel, Aarti
AU  - Patel A
AD  - GlaxoSmithKline, United Kingdom.
FAU - Tistaert, Christophe
AU  - Tistaert C
AD  - Janssen, Belgium.
FAU - Bevernage, Jan
AU  - Bevernage J
AD  - Janssen, Belgium.
FAU - Nguyen, Mai Anh
AU  - Nguyen MA
AD  - Johannes Gutenberg University of Mainz, Germany.
FAU - Lindley, David
AU  - Lindley D
AD  - AbbVie, Germany.
FAU - Carr, Robert
AU  - Carr R
AD  - AbbVie, Germany.
FAU - Rostami-Hodjegan, Amin
AU  - Rostami-Hodjegan A
AD  - University of Manchester, United Kingdom; Certara, Simcyp Division, United 
      Kingdom.
LA  - eng
PT  - Comparative Study
PT  - Evaluation Study
PT  - Journal Article
DEP - 20200814
PL  - Netherlands
TA  - Eur J Pharm Biopharm
JT  - European journal of pharmaceutics and biopharmaceutics : official journal of 
      Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
JID - 9109778
RN  - 0 (Pharmaceutical Preparations)
SB  - IM
MH  - Administration, Oral
MH  - Biopharmaceutics/methods/*standards
MH  - Clinical Trials as Topic/methods/standards
MH  - *Data Analysis
MH  - Databases, Factual/standards
MH  - Forecasting
MH  - Humans
MH  - Intestinal Absorption/*drug effects/physiology
MH  - *Models, Biological
MH  - Pharmaceutical Preparations/administration & dosage/*metabolism
MH  - Software/*standards
OTO - NOTNLM
OT  - Absorption
OT  - Biopharmaceutics
OT  - Modelling and simulation (M&S)
OT  - Oral bioavailability (F(oral))
OT  - Physiological-based pharmacokinetic (PBPK)
EDAT- 2020/08/18 06:00
MHDA- 2021/07/08 06:00
CRDT- 2020/08/18 06:00
PHST- 2020/01/08 00:00 [received]
PHST- 2020/06/12 00:00 [revised]
PHST- 2020/08/06 00:00 [accepted]
PHST- 2020/08/18 06:00 [pubmed]
PHST- 2021/07/08 06:00 [medline]
PHST- 2020/08/18 06:00 [entrez]
AID - S0939-6411(20)30241-1 [pii]
AID - 10.1016/j.ejpb.2020.08.006 [doi]
PST - ppublish
SO  - Eur J Pharm Biopharm. 2020 Nov;156:50-63. doi: 10.1016/j.ejpb.2020.08.006. Epub 
      2020 Aug 14.