AbbVie is a research-based global biopharmaceutical company committed to developing innovative, advanced therapies for some of the world's most complex and critical conditions. The company's mission is to use its expertise, dedicated people and unique approach to innovation to markedly improve treatments across four primary therapeutic areas: immunology, oncology, virology and neuroscience. But we do more than treat diseases. With ~30,000 employees and marketed products in more than 175 countries, we aim to make a remarkable impact on people’s lives.

The DMPK-BA organization plays a vital role in increasing probability of success of AbbVie's pipeline, supporting early Discovery and continuing through all phases of clinical development. We provide:

• Mechanistic understanding of ADME; in vitro ADME, CYP/transporter and biotransformation data
• Prediction of human exposure, formulation/food effects, DDI (PBPK modeling)
• FIH dose recommendation and efficacious dose regimen prediction
• Target assessment/quantification using proteo(geno)mics
• Preclinical and Clinical Biomarker, PK (small and large molecules), and Immunogenicity bioanalysis

• Mechanistic understanding of efficacy and safety endpoints through translational modeling and simulation (PK/PD; Quantitative System Pharmacology)

DMPK-BA is the driving force of Translational Science, bringing transformative medicines to patients.

Find out more about Amgen on their website:

• Amgen

Lilly focus internal research efforts primarily on four core therapeutic areas: specialty care, diabetes, oncology and animal health. They also continue to pursue innovative science and new opportunities beyond our targeted disease categories.

A member of the Roche Group, Genentech has been at the forefront of the biotechnology industry for more than 40 years, using human genetic information to develop novel medicines for serious and life-threatening diseases. Genentech has multiple therapies on the market for cancer & other serious illnesses.

The Drug Metabolism and Pharmacokinetics (DMPK) group at Genentech is dedicated to enabling the discovery, development and commercialization of safe and effective medicines by elucidating the absorption, distribution, metabolism, excretion and pharmacokinetic properties of small molecule drug candidates. We accomplish this through the application of state of the art technologies, leveraging both internal and external collaborations.

GSK are a science-led global healthcare company with a special purpose: to help people do more, feel better, live longer.

They have 3 global businesses that research, develop and manufacture innovative pharmaceutical medicines, vaccines and consumer healthcare products.

Janssen focus their efforts and resources where the need is high, the science is compelling and where they have the greatest opportunity to save and improve lives.

Merck is a leading science and technology company in healthcare, life science and performance materials. As the largest of Merck’s three business sectors, Merck Healthcare has about 20,000 employees around the world work in Europe, North America, Asia, Africa and Latin America and is dedicated to driving innovation in science and technology for real improvement of patients' lives.

The biopharma portfolio of the healthcare sector focuses on the therapeutic areas of oncology, neurology, immunology, fertility, general medicine and endocrinology.

Merck-sponsored project

PBPK models of gastrointestinal and hepatic cancers

Cancer patients are characterised by high drug exposure variability.

The aim of this project is to create virtual cancer patient populations, in order to understand the variability of drug metabolism in cancer patients, and predict the disease impact on the gastrointestinal and hepatic cancers.

This will be achieved firstly through the quantification of DMEs and transporters by using LC-MS/MS.

These measurements will be incorporated into PBPK models and the models will be validated by the assessment of the disease impact on small molecule anti-cancer drugs. The overall accomplishment will be the improvement of cancer population profiles in existing PBPK models.

Project by PhD student Areti Vasilogianni.

Supervisors: Dr Sheila-Annie Peters (Merck), Professor Amin Rostami, Dr Adam Darwich, Dr Jill Barber (CAPKR).

Find out more about Roche on their website:

• Roche

Find out more about Servier on their website:

• The Servier Group

Takeda Pharmaceuticals is a global company with a 236 year long, rich drug discovery and development history. Takeda always conducts drug discovery/ business based on its core values (Takeda-isms) and priorities.

Takeda-ism (integrity, fairness, honesty, perseverance) and the four priorities (patient, trust, reputation, business) are deeply ingrained in Takeda’s ways of working to ensure its commitment to quality and that Takeda does the right thing – at all times.

Takeda focuses on four major therapeutic areas including neuroscience, gastroenterology, vaccines, and oncology. An additional therapeutic area, rare diseases, will soon be added to Takeda’s portfolio. Takeda is and will continue to aspire to bring better health and a brighter future for people worldwide.

The project investigates the impact of inflammatory diseases (including cancer) on the suppression of metabolic enzymes (for example, CYP3A4) and transporters (for example, OATP1B1/3) at transcriptional and functional level in specific patient populations using liquid biopsies (LB).

This project also examines the effect of specific drugs on endogenous biomarkers (EB) of drug metabolizing enzymes/transporters. Endogenous biomarker and liquid biopsy data in the plasma samples from the same individuals will be leveraged to establish the relationship between the protein expression and functional activity of enzyme/transporters of interest in order to refine corresponding PBPK models in patient populations and address issues related to drug-drug or drug-disease interactions.

PI/researchers: Dr Nihan Izat (postdoc), Prof Aleksandra Galetin, Prof Amin Rostami

Funders/industry collaborators: CAPKR Consortium Members

Full title: Quantification of drug-metabolizing enzymes and transporters in healthy and diseased kidney, and the development of physiologically-based pharmacokinetic models of the kidney

The project aims to quantify drug metabolising enzymes (DME) and transporters in healthy and autosomal dominant polycystic kidney disease (ADPKD) to identify the expression of drug transporters and DMEs in ADPKD patients using global proteomic analysis, and use this data to generate a PBPK model of ADPKD population.

PIs/researchers: Dr Jill Barber (supervisor), Dr Zubida Al Majdoub and Prof Amin Rostami (co-supervisors), Annika Tillman (PhD student)

Funders/industry collaborators: DrugTRAIN: This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska Curie grant agreement No 955879

Physiologically-based pharmacokinetic modelling for aldehyde oxidase: establishing a translational PBPK framework for human aldehyde oxidase

The primary focus of the proposed project is to develop physiologically-based pharmacokinetic (PBPK) models for selected aldehyde oxidase (AO) substrates (and mixed aldehyde oxidase/ cytochrome P450 substrates).

The PBPK models will be informed and verified by in vitro data, quantitative protein abundance and clinical pharmacokinetics and drug-drug interaction (DDI) data.

The emphasis of the project is on elucidating the current gaps and limitations for quantitative translation of clearance and DDIs for AO substrate drugs within the PBPK framework. It is anticipated the research will lead to new approaches to delineate, quantify and predict the in vivo roles of hepatic and non-hepatic AO and other metabolic pathways (for example, cytochrome P450).

Expected outcome of the research will be a novel roadmap for in vitro-in vivo extrapolation linked with PBPK models for aldehyde oxidase-mediated metabolism and DDIs for application in drug discovery and development.

PIs/Researchers: Dr Daniel Scotcher, Prof Aleksandra Galetin, Dr Jill Barber, Prof Brian Houston, Dr Nihan Izat (post doc)

Funders/Industry collaborators: CAPKR Consortium Members

Full title: Integration of drug release and permeability with systems data relevant to PBPK model of nose-to-brain axis and verification using clinical data

This project aims to develop a nasal PBPK model including at least one pathway for nose-to-brain drug delivery. Furthermore, a prediction of local brain and systemic PK for selected target compounds will be performed.

Finally, model credibility will be established for the nasal PBPK model with available data from literature, from generated experimental data, or both.

PI/researchers: Dr Saeed Rezaa (postdoc), Dr Kayode Ogungbenro, Prof Amin Rostami, Prof Aleksandra Galetin

Funders/industry collaborators: FDA, IMIM Spain

Full title: Advancing the permeability-limited liver model with focus on CL passive diffusion and ft of dual hepatic transporter/CYP substrates

This project aims to improve determination of the rate-determining steps for dual substrates of hepatic transporter/CYP substrates, and IVIVE of passive diffusion clearance, together with fraction transported.

The project involves both experimental and modelling elements, with the aim to advance prospective prediction of transporter-mediated clearance and DDI using permeability-limited liver model with zonation.

PI/researchers: Dr Marie-Noelle Paludetto (postdoc), Prof Aleksandra Galetin, Dr Dan Scotcher (supervisor), Prof Brian Houston

Funders/industry collaborators: CAPKR Consortium Members

Full title: Quantification of the brain metabolizing enzymes, transporters and biomarkers in human cerebrospinal fluid (CSF) and brain tissue with neurodegenerative diseases

This project conducts proteomic analysis of blood brain barrier microvessels (both targeted and global analysis) alongside isolating exosomes from CSF and perform transcriptomics analysis using RNAseq.

The aim is to quantify abundance and assess interindividual variability of drug metabolizing enzymes, transporters and specific PD Biomarkers in matched exosomes of human cerebrospinal fluid (CSF) and neurodegenerative disease brain tissue

PI/researchers: Dr Isaebeau Vermeulen (postdoc), Dr Zubida Al Majdoub, Dr Kayode Ogungbenro, Prof Amin Rostami, Prof Aleksandra Galetin

Funders/industry collaborators: Servier

The project aims to use pre-clinical and clinical data to integrate PBPK (physiologically-based pharmacokinetic) and PopPK (population pharmacokinetic) modelling processes through a middle-out approach (due to the overlapping mechanistic approach in the PopPK and PBPK models), to better explain variability in patient populations, leading to more informed and robust predictions and efficient drug development.

PI/researchers: Dr Frederic Lusoli, Dr Kayode Ogungbenro, Dr Leon Aarons

Funders/industry collaborators: CAPKR Consortium Members

Quantification of human blood-brain barrier drug transporters and solute carriers in health and disease

The blood-brain barrier (BBB) remains a focal point of interest for many scientists who are working on approaches to deliver various therapeutic agents into the brain.

Alterations to BBB proteins can lead to changes in brain function affecting the susceptibility of the CNS to exposure to xenobiotics in the systemic circulation.

Dr Zubida's research focused on the quantification of transporters, enzymes and other proteins at BBB and measurement protein content of the microvascular fraction to populate PBPK model predicting drug disposition and the potential differences in health and disease.

Lead: Dr Zubida Al-Majdoub (working with Dr Jill Barber and Professor Amin Rostami)

Quantitative Systems Pharmacology Modelling for Translating Animal models of Neuroinflammation 

 Neurodegenerative diseases are becoming an increasing burden to healthcare systems with few impactful treatment options currently available.  Chronic neuroinflammation has been identified as a major contributing factor in many neurodegenerative diseases such as Alzheimer’s, amyotrophic lateral sclerosis, Parkinson’s and Huntington’s. 

A reason behind the difficulty in bringing effective drugs to market is the poor translatability of current pre-clinical animal and cellular models into human patients.  No one model can faithfully replicate the complex pathology that is observed in humans. 

The objective of this project is to develop a hybrid quantitative systems pharmacology (QSP) model with machine learning algorithms of the neuroinflammatory response in neurodegenerative diseases.  This model aims to relate the molecular determinants of disease progression observed in animals to human clinical outcomes.  

PIs/researchers: Dr Kayode Ogungbenro (supervisor), Dr Guy Meno-Tetang and Prof Amin Rostami (co-supervisors), Alex Foster-Powell (PhD student)

Funders/Industry collaborators: BBSRC and AstraZeneca

Quantitative Expression and Inter-Individual Variability of Skin Proteins Involved in Drug and Excipient Metabolism and Transporters Using Targeted and Label Free LC MS/MS Proteomics

 The project will generate the most comprehensive quantitative data set of xenobiotics metabolizing enzymes and transporters in human skin with indication of attributes defining population variability (e.g. race, sex, age). The information is essential for building robust models of dermal drug absorption and for understanding the influence of formulation ingredients (e.g. excipients, vehicle) with implication for developing faster and safer new complex generic dermal products. The data will be incorporated into the structure of physiologically based pharmacokinetic software (MechDermA PBPK, Simcyp) as proof of concept and will be used for predicting dermal absorption based on in vitro data under the newly established framework of virtual clinical trials in diverse population of patients.

PIs/researchers: Dr Jill Barber, Prof Amin Rostami, Dr Zubida Al-Majdoub, Sebastian Polak, Kanika Thakur (Certara’s Simcyp)

Funder: Department of Health and Human Services, U.S. Food and Drug Administration (FDA)

Industry collaborator: Certara’s Simcyp

Evaluating protein abundance vs. activity relationships of drug-metabolizing enzymes (CYP and UGT) in the human liver and small intestine

Current approaches for bottom-up prediction of intestinal and hepatic metabolic clearance, including biologically-associated variability, depend on assumption that enzyme activity is proportional to specific protein abundance. This activity-abundance proportionality is assumed to hold irrespective of the organ or patient characteristics. However, there is limited evidence to support this beyond the work done for intestinal and hepatic CYP3A4 (Gertz et al Drug Metab Dispos 2010, 38(7):1147-58).

The project aims to investigate relationship between expression and functional activity of major CYP and UGT drug metabolizing enzymes between human liver and gut. Using CAPKR’s expertise in functional and proteomic analysis, project aims to measure enzyme abundance and activity of specific probes in matched liver and intestinal samples obtained from the same human donors. Implications of the findings on the quantitative translation of drug clearance and drug-drug interactions will be investigated.

Leads: Dr Zubida Al-Majdoub (working with Dr Aleksandra Galetin (PI), Dr Jill Barber, Dr Daniel Scotcher, Professor Amin Rostami)

Funder: CAPKR consortium-sponsored project

Despite current knowledge of contributors to inter-individual variability in pharmacokinetics (such as drug enzyme and transporter genotypes, and age), heterogeneity in drug responses still confounds individualization of drug regimens. Orally administered drugs encounter gut microbiota in the intestine prior to absorption, potentially affecting pharmacokinetics either directly or indirectly through interacting with the host’s drug metabolizing enzymes and drug transporters.

This project, funded by Norwegian Research Council, is part of an interdisciplinary framework with the overarching aim of investigating optimization of drug therapy in obesity based on considerations of host-microbiome interplay. Using advanced computational approaches, this project will aim to amend existing physiologically-based pharmacokinetic (PBPK) models for healthy subjects in order to capture changes in obesity and any gut microbiome effect on key metabolizing enzymes and drug transporters, for example, CYP3A, P-glycoprotein and OATP1B1.

Once validated, these models will provide powerful quantitative translational tools for predicting drug-drug interaction risk in these patient cohorts.

PIs/researchers: Hari Kangne (PhD student), Aleksandra Galetin (PI), Kayode Ogungbenro, Dr Nihan Izat

Funders/industry collaborators: Norwegian Research Council

This project combines albumin-mediated uptake in vitro experiments, PBPK modelling and literature analysis to investigate changes to organic anion transporter 1/3 (OAT1/3) activity in case of drug-drug interactions and in renal impairment. Starting off with a retrospective analysis of published clinical data, a database of OAT1/3 substrates will be created and the effect of chronic kidney disease (CKD) on the activity of OAT1/3 will be evaluated.

The project will investigate the albumin-mediated uptake phenomenon and its impact on IVIVE of renal secretion and renal clearance of OAT1/3 substrates in healthy populations. In parallel, development of PBPK model for OAT1/3 endogenous biomarker and, clinical probe substrate and inhibitor will be performed to demonstrate application of biomarker-informed PBPK modelling to assess in vivo risk of OAT1/3 inhibition in early drug development.

Finally, extrapolation of in vitro OAT1/3 dataset and developed PBPK models to the CKD population will be performed by accounting for disease-related changes in protein binding and OAT1/3 activity to increase our confidence in predicting pharmacokinetics in this patient population.

PIs/researchers: Shawn Pei Feng Tan (PhD student), Prof Aleksandra Galetin, Prof Amin Rostami, Dr Daniel Scotcher

Funders/industry collaborators: Agency for Science, Technology and Research, Singapore

The MSc in Model-based Drug Development at emphasises mechanistic approaches for the assessment and prediction of pharmacokinetics and pharmacodynamics (PKPD), such as physiologically-based pharmacokinetics (PBPK).

Students will develop the modelling and simulation skills required during drug development, qualifying as a modeller with key skills in computational approaches in pharmacokinetics and pharmacodynamics. This includes experience of the R, Phoenix, NONMEM, MATLAB, Simcyp, and MONOLIX data analysis platforms.

The course also covers structured problems requiring theory and practical skills to solve typical problems that arise in drug development programmes.

The course is available as:

• a one-year full-time course with on-campus teaching;
• a two-year part-time course for off-campus distance learning students, particularly scientists in the pharmaceutical industries who want to expand their expertise.

Learn more and apply

Visit the course page for more information about the course, including a list of units, and details of how to apply:

• MSc Model-based Drug Development

CAPKR hosts students to undertake a research project that will further improve their understanding of pharmacokinetics and modelling. We also provide a framework of postgraduate research training in research council-funded doctoral training partnerships.

Visit the Faculty of Biology, Medicine and Health website to learn more about funded PhD programmes and see all PhD programmes.

Our CPD units are designed for science, engineering or mathematics graduates, and scientists linked to the pharmaceutical industry who wish to expand their expertise while working in the industry.

The units are taken from the MSc Model-based Drug Development course and are taught as standalone CPD courses in blocks of either 6 weeks (15 credits per unit) or 12 weeks (30 credits per unit). 

Students will develop the knowledge and skills required for making evidence-based decisions at various stages of drug development.

Learn more and apply

Visit the CPD course page for more information, including a list of available units, and details of how to apply:

• Model-based Drug Development (CPD)