Mobile menu icon
Mobile menu icon Search iconSearch
Search type
microbiology and pharmaceutical research background, 3d illustration

Centre for Applied Pharmacokinetic Research

Delivering the right dose of a prescribed medicine to the right patient

The Centre for Applied Pharmacokinetic research (CAPKR) is a consortium of academic researchers at The University of Manchester and ten industrial pharmaceutical companies.

Our mission is to understand what happens to drugs when they enter the body – where they go, how they are metabolised and how quickly. In particular, we seek to understand how differences of genetics, lifestyle and disease affect what happens to drugs.

This understanding leads to more appropriate drugs and dosing for each patient (so called 'precision medicine') and more economic use of drugs by the NHS and other healthcare providers.

What we do

  • We quantify the proteins responsible for the metabolism and transport of drugs in the body, by various proteomic methodologies, mainly based on tandem mass spectrometry.
  • We determine activities of human and animal drug metabolising enzymes and transporters using different in vitro systems. We use in silico models to extrapolate from in vitro to in vivo (IVIVE).
  • We use such models to predict pharmacokinetic parameters for different drugs in different groups of patients.
  • We determine effective, safe and economical dose regimes for different groups of patients.
Innovative technologies in medicine.
 

Our industry collaborators

The CAPKR industrial consortium was established in 1996 by Professor Malcolm Rowland at The University of Manchester to generate a centre of excellence in research and training of pharmacokinetics, and engage in problems of interest to the pharmaceutical industry.

Our current industry partners include:

AbbVie

AbbVie logo

 

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.

Amgen

Amgen logo.

 

Find out more about Amgen on their website:

Eli Lilly

Lilly logo

 

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.

Genentech

Genentech logo

 

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

GSK logo

 

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

 

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

MERCK logo

 

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).

Roche

Roche logo

 

Find out more about Roche on their website:

Servier

Servier logo.

 

Find out more about Servier on their website:

Takeda Pharmaceuticals

Takeda Pharmaceuticals logo

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.

Potential industrial partners

If you would like to work with us, please contact the centre directors Professor Amin Rostami and Professor Alex Galetin.

 

pharmaceutical factory woman worker operating production line at pharmacy industry manufacture factory
 

Featured projects

CAPKR has around 10 post-doctoral associates, 20 PhD students and several visitors working on various projects related to our mission. Here are just a few of them.

In vitro screening of chemotherapeutic treatments and target therapies for Pseudomyxoma peritonei (PMP)

In vitro screening of chemotherapeutic treatments and target therapies for Pseudomyxoma peritonei (PMP)

The aim of the project is to profile the characteristics of the tumours in PMP patients and seek out specific drug targets for PMP. Tumour and histologically normal peri-carcinomateous tissues, as well as plasma and drain fluid are collected from PMP patients undergoing cytoreductive surgery (CRS) and heated intraoperative peritoneal chemotherapy (HIPEC). Proteomic and miRNA measurements are used to identify existing drug targets suggested by the genomic/transcriptomic/proteomic characteristics of PMPs, and a particular focus is given on the upregulation of proteins that are known to be drug targets. A stepwise method to select drug candidates as well as appropriate methods for their subsequent mechanistic validation on the in vitro models generated will be developed.

PIs/Researchers: Dr Jill Barber, Prof Amin Rostami-Hodjegan, Dr Costas Demonacos, Dr Areti-Maria Vasilogianni (post doc)

Funding: CRUK Accelerator Award

The human blood-brain barrier

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)

Liquid Biopsy: Precision dosing of metabolically-cleared drugs

Development of techniques for precision dosing of metabolically-cleared drugs

Liver biopsies are required to assess abundance and activity of enzymes that contribute to the clearance of drugs and other xenobiotics. This can be invasive and alternative methods to enable precision dosing in the clinic are required.

We are therefore developing methods for the quantification of hepatic enzyme abundance in tissue using surrogate analytes in plasma. The approach involves quantifying RNA in isolated plasma exosomes.

Future assessment of specific plasma metabolites is planned.

Lead: Dr Brahim Achour (working with Professor Amin Rostami)

Industry collaborators: Certara, Thermo, Illumina

 

Physiologically-based pharmacokinetic modelling for aldehyde oxidase

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

3D microphysiological model of human kidney proximal tubule as in vitro tool

Currently there is a growing interest in employing advanced 3D systems, e.g. organ-on-a-chip technology, to study renal biology and toxicology and to mimic specific disease states due to its advantages compared to 2D systems.

These systems show promising physiological features and exhibit long-term viability (up to 28 days). However, the application of these novel technologies for mechanistic prediction of renal drug disposition and the translational value remains a challenge.

The objective of this project is to investigate different cellular platforms (in conjunction with mechanistic modelling) as predictive tools for investigating renal drug-drug interactions and nephrotoxicity, in particular associated with OAT1. Specific focus will be on Nortis ParVivo system and its feasibility to study drug transport in the proximal tubule via OAT and OCT transporters.

Postgraduate researcher/PhD student: Shawn Tan

Lead: Aleksandra Galetin and Amin Rostami

Industry collaborator: Janssen Pharmaceutica

Quantitative Systems Pharmacology Modelling for Translating Animal models of Neuroinflammation

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

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

The use of PKPD modelling to analyse real-world healthcare data

The use of PKPD modelling to analyse real-world healthcare data

Pharmaceutical regulators and clinical researchers have highlighted the need for dosage recommendations in special patient populations, such as the elderly, children and various disease conditions. The use of real-world healthcare data (RWD) has been suggested as a means to understand the pharmacology and dose-response/toxicity in special patient groups. Healthcare data poses unique challenges due to variable documentation practices, latent effects, nonrandom missingness, and ethical considerations. This project aims to carry out the necessary groundwork for pharmacological modelling of RWD. Several identified prerequisites will be examined: the availability of healthcare datasets in Sweden and the United Kingdom, their variable specifications, data requirements for pharmacological modelling, data management, sharing, and ethics. A workshop will be held to present the findings and discuss solutions with experts from various domains. This to produce a feasibility analysis and roadmap for pharmacokinetic/pharmacodynamic (PKPD) analysis of RWD.

PI/researchers: UoM – Dr Kayode Ogungbenro, Prof Leon Aarons; KTH – Adam Darwich

Funding: KTH Royal Institute of Technology and Stockholm University Joint Research Seed Fund

TRISTAN

Translational Imaging in Drug Safety Assessment

Imaging biomarkers, based on non-invasive techniques such as positron emission tomography (PET) and magnetic resonance imaging (MRI), offer potential for insights into toxicity issues early on in drug development. One of TRISTAN project aims is to validate the use of gadoxetate as MRI biomarker for assessment of hepatobiliary transporter mediated drug-drug interactions (work package 2).

CAPKR team will perform in vitro evaluation of hepatic uptake of gadoxetate and develop a physiologically based pharmacokinetic model for this imaging biomarker. CAPKR’s expertise in quantitative translation will support the mechanistic interpretation of the in vivo MRI data being generated for gadoxetate, including effects of various transporter inhibitors.

Lead: Dr Aleksandra Galetin (working with Dr Adam Darwich, Dr Kayode Ogungbenro, and Dr Daniel Scotcher)

Funding: Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 116106.

Inter-organ relationship between expression and activity of gut and liver enzymes

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

 

Highlight publications

CAPKR staff published 39 articles in the period October 2020 – October 2021. Browse a selection of our publications.

Liquid Biopsy Enables Quantification of the Abundance and Interindividual Variability of Hepatic Enzymes and Transporters

Title: Liquid Biopsy Enables Quantification of the Abundance and Interindividual Variability of Hepatic Enzymes and Transporters

Authors: Achour B, Al-Majdoub ZM, Grybos-Gajniak A, Lea K, Kilford P, Zhang M, Knight D, Barber J, Schageman J, Rostami-Hodjegan A

URL: https://doi.org/10.1002/cpt.2102 (2020)

Variability in individual capacity for hepatic elimination of therapeutic drugs is well recognized and is associated with variable expression and activity of liver enzymes and transporters. Although genotyping offers some degree of stratification, there is often large variability within the same genotype. Direct measurement of protein expression is impractical due to limited access to tissue biopsies. Hence, determination of variability in hepatic drug metabolism and disposition using liquid biopsy (blood samples) is an attractive proposition during drug development and in clinical practice. This study used a multi-“omic” strategy to establish a liquid biopsy technology intended to assess hepatic capacity for metabolism and disposition in individual patients.

Quantitative Proteomic Map of Enzymes and Transporters in the Human Kidney: Stepping Closer to Mechanistic Kidney Models to Define Local Kinetics.

Title: Quantitative Proteomic Map of Enzymes and Transporters in the Human Kidney: Stepping Closer to Mechanistic Kidney Models to Define Local Kinetics.

Authors: Al-Majdoub ZM, Scotcher D, Achour B, Barber J, Galetin A, Rostami-Hodjegan A

URL: https://doi.org/10.1002/cpt.2396 (2021)

The applications of translational modeling of local drug concentrations in various organs had a sharp increase over the last decade. With respect to the kidney, the models serve as a bridge for understanding animal vs. human observations related to renal drug disposition and any consequential adverse effects. However, quantitative data on key drug-metabolizing enzymes and transporters relevant for predicting renal drug disposition are limited. Using targeted and global quantitative proteomics, we determined the abundance of multiple enzymes and transporters in 20 human kidney cortex samples. This study extends our knowledge of pharmacologically relevant proteins in the kidney cortex, with implications on more prudent use of mechanistic kidney models under the general framework of quantitative systems pharmacology and toxicology.

Non-uniformity of changes in drug-metabolizing enzymes and transporters in liver cirrhosis

Title: Non-uniformity of changes in drug-metabolizing enzymes and transporters in liver cirrhosis: Implications for drug dosage adjustment

Authors: El-Khateeb E, Achour B, Al-Majdoub ZM, Barber J, Rostami-Hodjegan A

URL: https://doi.org/10.1021/acs.molpharmaceut.1c00462 (2021)

Liver cirrhosis is a chronic disease that affects the liver structure, protein expression, and overall metabolic function. Abundance data for drug-metabolizing enzymes and transporters (DMET) across all stages of disease severity are scarce. Levels of these proteins are crucial for the accurate prediction of drug clearance in hepatically impaired patients using physiologically based pharmacokinetic (PBPK) models, which can be used to guide the selection of more precise dosing. This study provides the biological rationale behind the absence of a single dose adjustment formula for all drugs in cirrhosis and demonstrates the utility of proteomics-informed PBPK modeling for drug-specific dose adjustment in liver cirrhosis.

Hepatic scaling factors for IVIVE of metabolic drug clearance in patients with colorectal cancer

Full title: Hepatic scaling factors for in vitro-in vivo extrapolation (IVIVE) of metabolic drug clearance in patients with colorectal cancer with liver metastasis

Authors: Areti-Maria Vasilogianni, Brahim Achour, Daniel Scotcher, Sheila Annie Peters, Zubida M. Al-Majdoub, Jill Barber, Amin Rostami-Hodjegan

https://doi.org/10.1124/dmd.121.000359

This study presents, for the first time, scaling factors for IVIVE of metabolic drug clearance in cancerous and matched histologically normal livers from colorectal cancer liver metastasis patients. The application of the measured scaling factors on PBPK simulations of various metabolically cleared drugs demonstrate the necessity of population-specific scaling for model-informed precision dosing in oncology.

3D illustration of colorectal cancer

Model-based drug-drug interaction extrapolation strategy from adults to children

Title: Model-based drug-drug interaction extrapolation strategy from adults to children – risdiplam in pediatric patients with spinal muscular atrophy

Authors: Cleary Y, Gertz M, Grimsey P, Günther A, Heinig K, Ogungbenro K, Aarons L, Galetin A and Kletzl H

URL: https://doi.org/10.1002/cpt.2384 (2021)

Risdiplam (Evrysdi) improves motor neuron function in patients with spinal muscular atrophy (SMA) and has been approved for the treatment of patients ≥2 months old. Risdiplam exhibits time-dependent inhibition of cytochrome P450 (CYP) 3A in vitro. While many pediatric patients receive risdiplam, a drug–drug interaction (DDI) study in pediatric patients with SMA was not feasible. Therefore, a novel physiologically-based pharmacokinetic (PBPK) model-based strategy was proposed to extrapolate DDI risk from healthy adults to children with SMA in an iterative manner.

This study provides comprehensive evaluation of the sensitivity of predicted CYP3A DDI on selected intestinal and hepatic CYP3A ontogeny functions, together with PBPK model-based strategy and general recommendations for DDI extrapolations in paediatric populations. The work illustrates application of this modelling framework for regulatory submission and its impact on risdiplam drug label and patient safety.

Physiologically Based Pharmacokinetic Modeling of Transporter-Mediated Hepatic Disposition of Imaging Biomarker Gadoxetate in Rats

Title: Physiologically Based Pharmacokinetic Modeling of Transporter-Mediated Hepatic Disposition of Imaging Biomarker Gadoxetate in Rats

Authors: Scotcher D, Melillo N, Tadimalla S, Darwich AS, Ziemian S, Ogungbenro K, Schütz G, Sourbron S, Galetin A

URL: https://doi.org/10.1021/acs.molpharmaceut.1c00206 (2021)

Physiologically based pharmacokinetic (PBPK) models are increasingly used in drug development to simulate changes in both systemic and tissue exposures that arise as a result of changes in enzyme and/or transporter activity. Verification of these model-based simulations of tissue exposure is challenging in the case of transporter-mediated drug-drug interactions (tDDI), in particular as these may lead to differential effects on substrate exposure in plasma and tissues/organs of interest. In this study, we developed a gadoxetate (a promising magnetic resonance imaging [MRI] contrast agent), PBPK model and explored the use of liver-imaging data to achieve and refine in vitro-in vivo extrapolation (IVIVE) of gadoxetate hepatic transporter kinetic data. The results of our study demonstrate the utility of organ-imaging data in evaluating and refining PBPK transporter IVIVE to support the subsequent model use for quantitative evaluation of hepatic tDDI.

Download a list of our publications from October 2020 - October 2021 (PDF, 562KB)

 

Our academics

Seven academics make up CAPKR, all providing complementary expertise in applied pharmacokinetic research.

Together they provide experience in both in vitro and in vivo systems, as well as computer-based pharmacokinetics and pharmacodynamics, and omics, especially proteomics and transcriptomics of human and animal tissue.

Professor Amin Rostami – Director of CAPKR

Amin Rostami

Amin is well-known for his contribution to translational modelling, such as physiologically-based pharmacokinetics (PBPK). 

He is the author of over 300 highly-cited articles, and serves on the editorial board of several journals. 

In 2017 he was listed as one of the world's most highly-cited researchers (in Pharmacology and Toxicology), and in 2020 he was in the top 0.06% of the highest cited researchers list by Elsevier (under 'Pharmacology/Pharmacy').

Amin collaborates with other members of CAPKR to deliver training for PhD students in involving proteomics, PBPK, clinical pharmacokinetics and pharmacodynamics and precision dosing.

View research profile

email: amin.rostami@manchester.ac.uk

 

 

Professor Aleksandra Galetin – Deputy Director

Aleksandra Galetin

Alex is the recipient of the 2012 ISSX European New Investigator Award. She is very active in the International Transporter Consortium Committee leading in PBPK/translational modelling of transporter kinetics and endogenous biomarkers for transporter drug-drug interactions.

Alex had a sabbatical in the US Food and Drug Administration's Office of Clinical Pharmacology where she provided expert advice on the PBPK modelling of drug-drug interactions and specific populations.

These research activities are also captured in her CAPKR projects.

View research profile

email: aleksandra.galetin@manchester.ac.uk

 

Professor Brian Houston – Advisor

Brian Houston

In recent years Brian has been particularly active through his research and numerous conference presentations in promoting the use of in vitro and in silico systems for predicting human metabolism and pharmacokinetics.

Brian is a member of the editorial boards of several scientific journals, has experience on national science funding bodies and is a consultant to a number of pharmaceutical companies.

He is a Fellow of the American Association of Pharmaceutical Scientists (AAPS) and received the International Society for Study of Xenobiotics (ISSX) 2014 European Scientific Achievement Award.

He has supervised over 60 graduate students. His research publications in the area of drug metabolite kinetics in vivo and in vitro exceed 200 and are highly cited. He was named as a Thomson Reuters Highly Cited Researcher in 2015, ranking among the top 1% most cited scientists in his subject field (Pharmacology and Toxicology) earning him the mark of exceptional impact.

View research profile

email: brian.houston@manchester.ac.uk

 

Dr Jill Barber – Proteomics Lead

Jill Barber

Like many NMR spectroscopists, Jill became a mass spectrometrist in middle age, specialising in quantitative proteomics, particularly as applied to drug metabolism and disposition. 

Her group is able to quantify enzymes and transporters in a variety of tissues and thereby feed data-hungry quantitative systems pharmacology models of health and disease.

Apart from research, Jill has won every teaching excellence award the University offers, and is also a National Teaching Fellow.

View research profile

email: jill.barber@manchester.ac.uk

 

 

Dr Zubida Al-Majdoub - Proteomics Co-Lead

Dr Zubida Al-Majdoub

Zubida has research interests in pharmaco-‘omics’ with specific expertise in quantitative proteomics and transcriptomics as applied to pharmacologically-relevant pathways involved in drug metabolism and drug transport.

Her work was among the ‘first’ that contributed to the application of QconCAT technology to study ADME (absorption, distribution, metabolism, and excretion) proteins. This technology is now world leading in the field of Quantitative ADME to support mechanistic modelling and simulation.

She is also interested in liquid biopsy approach to monitor expression of ADME proteins and inter-individual variability.

Dr Kayode Ogungbenro – Modelling Lead

Kayode Ogungbenro

Kayode Ogungbenro is a Lecturer in Cancer Pharmacometrics and an Honorary Clinical Scientist at The Christie NHS Foundation Trust, Manchester. 

His research activities within CAPKR are centred around population pharmacokinetics for top-down (empirical) and bottom-up (PBPK) models.

He is also interested in modelling pharmacodynamic data, optimal design and sample size calculations of population PK studies, population pharmacokinetics in special population (children) and computer aided clinical trial simulation.

Kayode is also the Director of MSc in Model-Based Drug Development which is based within CAPKR.

View research profile

email: kayode.ogungbenro@manchester.ac.uk

 

Professor Leon Aarons – Pharmacokinetics and Pharmacodynamics Lead

Leon Aarons

Leon's major research interests lie in the area of pharmacokinetic and pharmacodynamics modelling.

He has a worldwide reputation in the area of population pharmacokinetics with applications in drug development and drug utilisation in a number of disease states including tropical diseases such as malaria.

Leon is a member of the British Pharmacological Society, a founding member of the United Kingdom Pharmacokinetic Discussion Group and a member of the organising committee of the Population Approach Group Europe.

He is on the editorial boards of a number of journals including Emeritus Editor of the Journal of Pharmacokinetics and Pharmacodynamics.

He has supervised more than 40 postgraduate students, many of which have gone onto positions in academia and the pharmaceutical industry. For more than 20 years he has been teaching pharmacokinetics and pharmacodynamics courses in Europe, Australasia, the United States and Africa.

View research profile

email: leon.aarons@manchester.ac.uk

 

Dr Daniel Scotcher

Dan has research interests in quantitative translation of in vitro data to predict in vivo pharmacokinetic endpoints. He has particular expertise in the use of physiologically-based pharmacokinetic (PBPK) modelling to mechanistically describe and predict drug disposition in health and disease.

After a brief time working in the pharmaceutical industry, Dan completed his PhD at the University of Manchester in 2016, and then visited the US Food and Drug Administration as an ORISE research fellow. He returned to Manchester as a Research Associate working on an Innovative Medicines Initiative project on Translational Imaging in Drug Safety Assessment, and was subsequently appointed as Lecturer in 2019.

Dan is Deputy Director of the MSc in Model-Based Drug Development, which is based within CAPKR.

Students studying
 

MSc and CPD courses

MSc and CPD courses in model-based drug development are available at The University of Manchester.

Our current industry partners include:

Students learn from experts at CAPKR and the University's Division of Pharmacy and Optometry.

MSc Model-based Drug Development

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:

Continuing professional development

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:

Events and conferences

Find out more about events and conferences with CAPKR involvement.

Past events

Celebrating CAPKR academic staff promoted in 2020

CAPKR is delighted to highlight the promotions of two of our academics in 2020, in recognition of their research excellence, leadership and inspirational teaching.

Professor Aleksandra Galetin, Deputy Director for CAPKR, was promoted to a Chair. Alex has published >90 research papers on pharmacokinetics and drug transporters, mentored over 35 PhD students, and was a meeting chair of the 12th International ISSX Meeting (Portland, Oregon; July 2019).

Dr Kayode Ogungbenro, Modelling Lead for CAPKR and Director of MSc in Model-Based Drug Development, was promoted to Senior Lecturer. Kay has published extensively on model-informed precision dosing and optimal study design, particularly relating to oncology and paediatric applications.

We are sure you will join us in our many congratulations to both Alex and Kay on their well-deserved achievements, and we look forward to their continued success.

ISSX2019

28 - 31 July 2019

Alex Galetin was in Portland, Oregon for the 12th International ISSX Meeting.

ISSX2019 logo

Festschrift

24 May 2019

A celebration of Professor Brian Houston's career on his retirement, we hosted a one day symposium, "Festschrift".

Read a blog post about this event.

Contact us

Get in touch to discuss collaborating now.

Contact one of the academic leads listed above.

For general enquiries please email capkr@manchester.ac.uk.