Data sources and software for PBK modelling
Physiologically-Based Kinetic (PBK) modelling require a great deal of information for parameterisation, regarding both chemical-specific as well physiological and anatomical information.
There has been previous collations of such resources and the information on these pages has largely been adapted and updated from:
- 'In silico resources to assist in the development and evaluation of physiologically-based kinetic models' (2019) Computational Toxicology 11, 33-49.
- 'Guidance document on the characterisation, validation and reporting of Physiologically Based Kinetic (PBK) models for regulatory purposes', OECD Series on Testing and Assessment, No. 331, OECD Publishing, Paris.
Data sources
There are many data sources available to assist in PBK modelling.
Please note:
Many of the resources identified below will appear more than once in the lists.
For example, resources such as ADMETlab, SwissADME, etcetera, provide predictions for both physico-chemical properties and ADME properties.
Faq Items
Resources for physico-chemical properties (databases and predictive software)
Resource: ACD / Percepta (ACD Labs)
Properties/information: Log P; log D; pKa; Abraham solvation parameters (relating to hydrogen bonding ability, polarizability, volume and partitioning)P
Resource: ADME SARfari (EMBL-EBI)
Properties/information: Log P; log D (reports values from ACD); PSA; M,P
Resource: ADMETlab
Properties/information: Log P; log D; log S
Resource: ADMET Predictor (Simulations Plus)
Properties/information: Log P; log D; pKa; diffusion coefficient; air: water partition coefficient; pH dependent solubility; solubility in gastric/intestinal fluid (fed and fasted states)
Resource: ALOGPS 2.1 (Virtual Computational Chemistry Laboratory)
Properties/information: Log P; log D; water solubility; pKa P
Resource: BioByte (Bio-Loom)
Properties/information: Log P, log D, pKaP,M
Resource: ChemIDplus Advanced
Properties/information: Log P, pKa, solubility, vapour pressure, m.ptM,P
Resource: ChemSpider (Royal Society of Chemistry)
Properties/information: Log P; water solubility, pKa, vapour pressure, Henry’s law constantM,P
Resource: Chemaxon
Properties/information: Log P; log D; hydrophilic:lipophilic balance; water solubility; hydrogen bond donor / acceptor; pKaP
Resource: Corina Symphony (MN-AM)
Properties/information: Log P; hydrogen bond donor / acceptor parametersP
Resource: Computational Toxicology Dashboard
Properties/information: Log P, m. pt, b. pt, vapour pressure, et ceteraM,P
Resource: EPI Suite (US-EPA): MOE (Molecular Modelling Environment)
Properties/information: Log P; water solubility, vapour pressure, Henry’s law constantM,P
Resource: MOE (Molecular Modelling Environment)
Properties/information: Calculates >400 molecular descriptors including physicochemical properties, Topological Polar Surface Area (TPSA), log P, log D, pKa, electronic effects such as hydrogen bonding capacity, partial charges, dipole moment, et cetera.
Resource: Moka Molecular Discovery
Properties/information: pKaP
Resource: Molinspiration
Properties/information: Log P; hydrogen bond donors / acceptors; TPSA; volume
Resource: OECD QSAR toolbox
Properties/information: Multiple physicochemical propertiesM,P
Resource: PubChem Open Chemistry database
Properties/information: Multiple physicochemical properties including log P, TPSA, water solubility, pKa, vapour pressureM,P
Resource: Schrödinger EPIK QikProp
Properties/information: pKa; Log P; water solubility
Resource: SwissADME
Properties/information: Multiple physicochemical properties including log P (various methods of calculation), water solubility, TPSA; no. hydrogen bond donors / acceptorsP
Resources for ADME properties (databases and predictive software)
Resource: ACD/Percepta
Properties/information: Estimates multiple ADME-PK related parameters including absorption, bioavailability, Cp (T), Tmax and Cp (max), AUC, Pgp substrate specificity, Vd, protein binding. Blood Brain Barrier (BBB) penetration, et cetera.
Resource: ADME database; Fujitsu Global
Properties/information: Interactions of substances with Phase I and II metabolising enzymes and drug transporters; database of kinetic parameters – in vitro assay model (Km, Vmax, Ki, Ks, efficiency, IC50, EC50, t½, et cetera).
Resource: ADMETlab
Properties/information: Human intestinal absorption; Caco-2 permeability; P-gp / CYP substrates and inhibitors; bioavailability; plasma protein binding; BBB partitioning; volume of distribution; t½ , clearance.
Resource: ADMET Predictor (Simulations Plus)
Properties/information: Permeability (skin, cornea, gastro-intestinal tract, BBB); interactions with OATP1B1 and P-gP; plasma protein binding; blood:plasma ratio, volume of distribution; fraction unbound in microsomes, et cetera).
Resource: admetSAR 3.0: Resource
Properties/information: Dataset for ADMET properties curated from literature; ADMET Simulator also predicts approx. 50 relevant ADMET endpoints. (Human intestinal absorption, bioavailability, volume of distribution, plasma protein binding, clearance, Ki IC50, et cetera).
Resource: ADME SARfari (EMBL-EBI)
Properties/information: Identifies ADME targets; finds pharmacokinetic data for input chemical or similar compounds.
Resource: ADMETNet
Properties/information: Depicts pharmacokinetic pathways for drugs; provides data such as half-life, free fraction in plasma bioavailability, volume of distribution, et cetera.
Resource: ARC fish
Properties/information: Fish whole-body in vivo biotransformation rate.
Resource: ARC fish dietary
Properties/information: Fish dietary bioaccumulation and toxicokinetics.
Resource: BIOVIA Metabolite: BIOVIA (formerly Accelrys)
Properties/information: Compilation of in vitro and in vivo metabolic data from literature, conference proceedings and New Drug Applications.
Resource: Brenda
Properties/information: Extensive database of Vmax, Km, Kcat and other parameters related to enzyme kinetics.
Resource: Computational Toxicology Dashboard
Properties/information: ADME data to be included in this database (ongoing).
Resource: Cytochrome P450 Drug Interaction Table
Properties/information: List of drugs acting as substrates, inhibitors (partial ranking as to weak, moderate or strong) and inducers of CYP enzymes - 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A4,5,7.
Resource: DIDB - Metabolism and Transport Drug Interaction Database
Properties/information: In vitro and in vivo drug interaction data from literature and New Drug Applications (NDA).
Resource: DrugBank
Properties/information: Key ADME properties for drugs, for example % oral absorption, volume of distribution, protein binding, metabolic information, t ½ , clearance, et cetera.
Resource: Drug Metabolism and pharmacokinetics Analysis Platform (DruMAP)
Properties/information: An online tool for the prediction of fraction unbound (fu,p value, fu, brain value), fraction absorbed (Fa), Papp (permeability coefficient for Caco-2), and D-Sol (solubility near pH 7 by dried DMSO method).
Resource: e-PK gene
Properties/information: Information on the impact of genetic variation on parent compound pharmacokinetics (for example changes in AUC, Cl or Cmax for different populations).
Resource: EDETOX database
Properties/information: A database of in vitro and in vivo skin penetration data for many compounds, including information on skin type, area and vehicle.
Resources:
- EURL ECVAM collection – JRC data catalogue (biokinetics databases)
- EURL ECVAM Fish In Vitro Intrinsic Clearance Database
- EURL ECVAM Fish In Vivo Biotransformation Database
- EURL ECVAM in vitro hepatocyte clearance and blood plasma protein binding dataset for 77 chemicals
- EURL ECVAM Rodent In Vitro Intrinsic Clearance Database
- EURL ECVAM Rodent In Vivo Biotransformation Database
Properties/information: Databases with in vitro or in vivo information on fish and rodent clearance and biotransformation. And in vitro human data on hepatic clearance and fraction unbound for 77 chemicals.
Resource: Evolvus: Microsomal Stability Database
Properties/information: Liver microsome stability assay data (ClINT and t½) for drugs and drug-like compounds curated from literature for rat, mouse, human and dog).
Resource: Goodman and Gilman’s The Pharmacological Basis of Therapeutics 13th Edition
Available from: McGraw-Hill Publishers (2017) ISBN-13: 978-1259584732
Properties/information: Appendices provide key pharmacokinetic data for commonly used drugs, for example oral bioavailability, urinary excretion, % bound in plasma, clearance, volume of distribution, half-life, Tmax and Cmax.
Resource: Hazard Evaluation Support System and Integrated Platform (HESS)
Properties/information: Metabolic maps and ADME data for humans and rats.
Resource: KinParDB European Commission Joint Research Centre
Properties/information: Kinetic parameters (for example clearance, half-life, AUC) for 100 diverse chemicals.
Resource: Laboratory of Molecular Modeling and Design (LMMD) Datasets
Properties/information: ADME databases curated from the literature with information on blood brain barrier (BBB) partitioning, human intestinal absorption, P450 inhibitors and non-inhibitors.
Resource: UFZ-LSER online database
Properties/information: Calculates partition coefficients from a CAS or SMILES.
Resource: The Merck Index Online
Properties/information: Provides links to original publications for individual drugs, including detailed reports for pharmacokinetics.
Resource: METRABASEF
Properties/information: Data on interactions between chemicals and proteins relating to metabolism and transport; 20 transporters and 13 CYP enzymes; identifies substrates and non-substrates / inhibitors and inducers.
Resource: Obach et al., 2008
Properties/information: Clinical IV data.
Resource: OECD QSAR toolbox
Properties/information: Encompasses a collation of databases including data on plasma protein binding, absorption, rat and human metabolic data – skin and liver.
Resource: Online chemical modelling environment - OCHEM
Properties/information: Datasets for many ADME properties (for example absorption, BBB partitioning, Caco2 permeability, log P, log D, water solubility, plasma protein binding, IC50, CYP Inhibition, P-gp substrate activity; tissue:blood partition coefficients and time dependent tissue-drug concentrations.
Resource: PharmaInformatic: PACT-F / PPB-DB
Properties/information: PACT-F provides bioavailability data for humans (from clinical trials) and preclinical animal studies. PPB-DB provides protein binding information.
Resource: PharmaPendium: Elsevier
Properties/information: ADME information searchable by terms such as % absorption, bioavailability, cell / protein binding metabolic transformation, tissue distribution, volume of distribution, clearance, half-life; humans, birds, fish and mammals.
Resource: pkCSM
Properties/information: Caco-2 / skin permeability, HIA, P-gP / CYP substrate / inhibitor; clearance, renal OCT2 substrate; volume of distribution, BBB permeability, fraction unbound in plasma.
Resource: QikProp
Properties/information: Predicts ADME relevant properties (for example blood brain partitioning, protein binding Caco-2 and MDCK permeability).
Resource: SwissADME
Properties/information: Multiple ADME–related properties including GI absorption, BBB penetration, skin penetration, interactions with P-gP and CYPs, drug-likeness characteristicsP
Resource: TRANSFORMER
Properties/information: Information on metabolism and transport of compounds in humans.
Resource: UCSF-FDA Transportal
Properties/information: Information on transporter expression, location, substrates, inhibitors and interactions.
Resource: US FDA drug database - drugs@fda (Orange Book)
Properties/information: In vitro and in vivo ADME data
Resource: VolSurf
Properties/information: Creates 128 molecular descriptors from 3D Molecular Interaction Fields (MIFs) related to ADME.
Resource: Sayre et al., 2020
Properties/information: Database of pharmacokinetic time-series data and parameters for 144 environmental chemicals.
PBK Modelling Software and related mathematical/simulation tools
Resource: CAKE
Brief summary of capabilities: Computer Assisted Kinetic Evaluation (CAKE) implements the FOCUS Kinetics and NAFTA guidance for estimating degradation kinetics for pesticides in environmental fate studies.
Resource: Cloe via Cyprotex
Brief summary of capabilities: Predicts concentration-time profiles in plasma and 14 organs/tissues using in vitro ADME and physicochemical data; models available for human, rat and mouse.
Resource: Cosmos KNIME workflow
Brief summary of capabilities: Physiologically-Based Kinetic (PBK) models to simulate concentration-time profiles and internal dose metrics for dermal or oral exposure scenarios.
Resource: High Throughput Toxicokinetics (Httk)
Brief summary of capabilities: Provides data tables and functions for simulation; facilities to parameterise PBK and one-compartment TK models for multiple chemicals and species; in vitro to in vivo extrapolation of HTS data; models can be exported for use with other simulation software.
Resource: GastroPlus via Simulations Plus, Lancaster, CA
Brief summary of capabilities: Comprises 10 modules including: PBPKPlus – enables PBPK modelling and IVIVE, can be parameterised for different disease states and age groups. ADMET Predictor – predicts physicochemical and ADME properties. Additional Dosage Routes – simulates oral cavity, dermal, pulmonary ocular and intramuscular administration. PKPlus – estimates PK parameters.
Resource: IndusChemFate (CEFIC LRI)
Brief summary of capabilities: Generic PBK model (first tier or screening level tool); estimates tissue body fluid concentrations following oral, dermal or inhalational exposure to volatile or semi-volatile chemicals.
Resource: MEGen
Brief summary of capabilities: Web application to generate PBK model equations; parameters may be retrieved from the integrated database or obtained from literature; output available in MATLAB, MCSim, R or other format.
Resource: PBPK Model - CEMC - Trent University
Brief summary of capabilities: The Canadian Centre for Environmental Modelling and Chemistry; Excel-based PBPK spreadsheet, parameterised for human male.
Resource: Simcyp® PBPK Simulator | PBPK Modeling Software | Certara
Brief summary of capabilities: PBK modelling and simulation platform; links in vitro data to in vivo ADME to predict PK/PD interactions for small molecules and biologics. Incorporates databases of genetic, physiological and epidemiological information to enable simulation of different populations (includes modules for paediatrics and rat, dog and knock-out mouse). Predicts ADME parameters such as oral, dermal, pulmonary absorption, clearance. Includes: ADAM (advanced dissolution, absorption and metabolism) model – predicts variability in bioavailability using physicochemical properties and in vitro data; dissolution (from various dosage forms) for oral absorption; models also available for skin and pulmonary absorption; BBB partitioning, metabolism, clearance, et cetera.
Resource: PK-Sim and MoBi via Open Systems Pharmacology Suite (Bayer)
Brief summary of capabilities:
PK-Sim: PBK modelling tool with integrated database of anatomical and physiological parameters for humans, mouse, rat, dog and monkey. Uses interchangeable building blocks to enable alternative scenarios to be considered, for example changing from animal model to human population or i.v. dose to controlled release.
MoBi: Software for multiscale physiological modelling and simulation. A range of biological models can be imported (for example PBK model imported from PK-Sim) or developed de novo; Software is compatible with Matlab and R.
Resource: PLETHEM (Population Lifecourse Exposure-To-Health-Effects Model) via ScitoVation
Brief summary of capabilities: Open source R package incorporating: a generic 11 compartment diffusion limited PBPK model; a high-throughput IVIVE model to extrapolate in vitro measured point of departure to equivalent exposures; an in-vitro to in-vivo model to extrapolate in vitro measured metabolism values to predicted in vivo values; population variability modelling; databases of age-dependent physiological and metabolic parameters; QSAR models to estimate partition coefficient.
Resource: Monolix (Lixoft)
Brief summary of capabilities: Publicly available for non-commercial purposes - Monolix is the most advanced and simple solution for non-linear mixed effects modeling (NLME) for pharmacometrics. It is based on the SAEM algorithm and provides robust, global convergence even for complex PK/PD models. Monolix is used for preclinical and clinical population PK/PD modeling and for Systems Pharmacology. Monolix is widely used by academia, the pharmaceutical industry as well as the US regulatory agencies.
Resource: Magnolia – Software for Mathematical Modeling and Simulation
Brief summary of capabilities: Magnolia provides the tools for developing models using an equation-based modeling language, scripting the execution of simulations using either the Python programming language or a simple command-based language.
Resource: MCSimMod Journal of Open Source Software: MCSimMod: An R Package for Working with Ordinary Differential Equation Models Encoded in the MCSim Model Specification Language
Brief summary of capabilities: flexible tool for implementation and application of PBPK and other ordinary differential equation (ODE) models. Allows users to define a model in MCSim, translate to C language, compile the C model to obtain machine code and then perform model simulations by writing R scripts that use the compiled code
Resource: NONMEM | Nonlinear Mixed Effects Modelling | ICON plc
Brief summary of capabilities: NONMEM – generic package for simulating/fitting data; PREDPP provides subroutines for predicting PK/PD data.
Resource: WinNonlin Non-Compartmental Analysis Software | Phoenix WinNonlin®
Brief summary of capabilities: WinNonlin – Industry standard integrated tool for non-compartmental analysis, PK/PD modelling; NLME – non-linear mixed effect modelling and simulation software
Resource: R-Vis AIMT7: R-Vis – Open Access PBPK Modelling Platform – Cefic-Lri
Brief summary of capabilities: Open source syntax R or C++ for the analysis of structure and performance of PBPK models
Resources for physiological and anatomical data
Resource: Abduljali et al., 2012
Properties/information: Key parameters for PBK modelling in pregnancy according to gestational age.
Additional information: Integration of data from extensive literature review of changes in anatomical, physiological and metabolic parameter changes during normal pregnancy.
Resource: Abduljali et al., 2017
Properties/information: Key biometric / morphological and compositional parameters to develop PBK models for a foetus at different gestational ages.
Additional information: Integration of data from extensive literature review providing data on size, height, weight, surface area, abdominal and head circumference, body composition.
Resource: Ball et al., 2013
Properties/information: PBK model structure for blood brain barrier (BBB) penetration based on literature review of existing PBK models for CNS.
Additional information: Includes evaluation of the applicability of in-vitro-in vivo extrapolation in PBK models for BBB penetration.
Resource: Brown et al., 1997
Properties/information: Physiological and anatomical parameter reference values (and ranges for values) for mice, rats, dogs and humans. Organ weights, composition, regional blood flows, volumes, cardiac output, respiratory parameters, etcetera.
Additional information: A comprehensive, key reference source for physiological and anatomical reference values in multiple species, expanding upon previous data collations and providing information on potential variability of the parameters.
Resource: Darwich et al., 2014
Properties/information: Enterocyte turnover in humans, rabbits, guinea pigs, rats, hamsters and mice.
Additional information: Collation of enterocyte turnover values in different species; turnover influences level of metabolising enzymes in gut wall which can be particularly relevant in drug-drug interactions.
Resource: Davies, B and Morris, T., Physiological Parameters in Laboratory Animals and Humans | Pharmaceutical Research | Springer Nature Link
Resource: Drozdik M et al Protein abundance of clinically relevant multidrug transporters along the entire length of the human intestine. Mol Pharm 2014 Oct 6;11(10):3547-55. Protein abundance of clinically relevant multidrug transporters along the entire length of the human intestine - PubMed
Resource: Gentry et al., 2005
Properties/information: Physiological values for PBK modelling (organ weights / volumes, ventilation, food / water intake, blood flows, bile flow, creatinine clearance, glomerular filtration rate) in neonatal and young rats and mice.
Additional information: Physiological parameters collated from literature reports are available in database format upon request to the corresponding author.
Resource: Gaohua et al., 2015
Properties/information: Organ model structures, anatomical and physiological data for lung.
Additional information: Model developed to predict pharmacokinetics of anti-tuberculosis drugs in lung. Model embedded within Simcyp simulator.
Resource: Gaohua et al., 2017
Properties/information: Model structure and parameters for a four-compartment permeability-limited PBK model for brain.
Additional information: Model performance investigated using paracetamol and phenytoin; Model embedded within Simcyp simulator.
Resource: Hall et al., 2011
Properties/information: Organ volumes, blood volumes and blood flow rates for mice, rats, rhesus monkeys, pigs and humans.
Additional information: The paper describes the development of a whole-body physiologically-based framework that uses novel physiological scaling laws to improve interspecies extrapolation.
Resource: Heikkinen et al., 2015
Properties/information: Quantified levels of cytochrome P450 and uridine diphosphate glucuronosyltransferase enzymes in Beagle dog liver and intestine.
Additional information: Enables comparison of enzyme levels between humans and dogs to assist interspecies scaling of pharmacokinetic properties.
Resource: ICRPP
Properties/information: Age and gender-specific anatomical and physiological reference values.
Additional information: A publication of the International Commission on Radiological Protection (ICRPP) to provide inputs for dosimetry calculations.
Resource: Interspecies databaseF
Properties/information: Anatomical, physiological and biochemical data for mouse, rat, rabbit, dog, monkey and pig.
Additional information: Developed by National Institute for Public Health and the Environment (RIVM) and the Dutch Ministry of Health, Welfare and Sports; provides physiological parameters for mouth, oesophagus, stomach, small and large intestine, liver, gallbladder, kidney and lung compiled from literature.
Resource: Johnson et al., 2005
Properties/information: Models for liver volume from birth to adulthood.
Additional information: Meta-analysis of published data / models collated from 5,036 subjects including investigation of covariates (age, gender, ethnicity).
Resource: Kararli TT (1995) Comparison of the gastrointestinal anatomy, physiology, and biochemistry of humans and commonly used laboratory animals;Biopharmaceutics and Drug Disposition | Pharmacology Journal | Wiley Online Library
Resource: Lautz et al (2021)
Properties/information: PBK model data for farm animals.
Additional information: Generic physiologically based kinetic modelling for farm animals: Part I. Data collection of physiological parameters in swine, cattle and sheep.
Resource: Li M et al Physiological parameter values for physiologically based pharmacokinetic models in food-producing animals. Part III: Sheep and goat
J Vet Pharmacol Ther, 2021 Jul;44(4):456-477; Physiological parameter values for physiologically based pharmacokinetic models in food-producing animals. Part III: Sheep and goat - PubMed
Resource: Lin, Z et al Physiological parameter values for physiologically based pharmacokinetic models in food-producing animals. Part I: Cattle and swine J Vet Pharmacol Ther. 2020 Sep;43(5):385-420. Physiological parameter values for physiologically based pharmacokinetic models in food-producing animals. Part I: Cattle and swine - PubMed
Resource: Lu et al (2016) PBK Knowledgebase
Properties/information: Corpus of information on PBK models for 307 chemicals published in literature.
Additional information: Enables identification of “similar” compounds that may serve as templates for PBK models; provides references for existing published models.
Resource: Mouly S and Paine MF, P-glycoprotein increases from proximal to distal regions of human small intestine - PubMed Pharm Res 2003 Oct;20(10):1595-9.
Resource: National Center for Health StatisticsF
Properties/information: Growth charts for 0-2 yrs and over 2yrs (length, height, BMI, head circumference).
Additional information: Links to World Health Organisation growth charts for 0-2yrs and United States Centers for Disease Control and Prevention growth charts for older than 2yrs.
Resource: Pilari et al., 2017
Properties/information: Organ model structures, anatomical and physiological data for testes and thyroid.
Additional information: Model validated using data for fentanyl, alfentanil, omadacycline, amiodarone, desethylamiodarone, propylthiouracil.
Resource: Price et al., (2003)
Properties/information: Volumes and blood flows for a range of organs and tissues, cardiac output and inhalation rate.
Additional information: Database with accompanying software for retrieving physiological parameters for PBK modelling accounting for inter-individual variation.
Resource: Thomson et al 2009
Properties/information: Age-specific organ volumes, blood flows , glomerular filtration rates for healthy and healthy-impaired elderly subjects.
Additional information: Physiological parameter values collated from 155 publications available as a Microsoft ACCESS database.
Resource: Tylutki et al., 2015
Available from: Biopharm. Drug Dispos. 36: 337–351 (2015) DOI: 10.1002/bdd.1944DOI: 10.1002/bdd.1944
Properties/information: Cardiac distribution of >200 drugs.
Additional information: Drug concentrations in cardiac tissue obtained from cardiac surgery and forensic study data.
Resource: United States Food and Drug Administration (updated 2023) Drug Development and Drug Interactions | Table of Substrates, Inhibitors and Inducers | FDA https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers
Resource: US EPA Physiological Information Database (PID)F
Properties/information: Physiological parameter values for humans and laboratory animals across life stages.
Additional information: Database (Microsoft ACCESS) created using data collated from extensive literature search and quality assured by independent contractor. Also available via HERO website.
Resource: Wang Y-S et al Physiological parameter values for physiologically based pharmacokinetic models in food-producing animals. Part II: Chicken and turkey J Vet Pharmacol Ther, 2021 Jul;44(4):423-455 Physiological parameter values for physiologically based pharmacokinetic models in food‐producing animals. Part II: Chicken and turkey
Resource: Zakaria et al., 2018
Properties/information: Model structure and parameter values for a four-compartment PBK model for brain.
Additional information: A region specific PBK model for brain developed using compartments for frontal cortex, hippocampus, “rest-of-brain” and cerebrospinal fluid.