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School of Pharmacy and Pharmaceutical Sciences

Professor Leon Aarons BSc, MSc, PhD

Photograph of Leon Aarons

Professor of Pharmacometrics

School of Pharmacy and Pharmaceutical Sciences
Stopford Building
Oxford Road
Manchester
M13 9PT

 

Research

Population pharmacokinetics and pharmacodynamics Computer aided clinical trial design Optimal design for population pharmacokinetic and pharmacodynamic studies

Population pharmacokinetics and pharmacodynamics

Population pharmacokinetics (PK) and pharmacodynamics (PD) aims to investigate and quantify PK/PD differences between patients. The sources of this variability include genetics, demographic differences, drug-drug interactions and disease state. Having identified sources of variability it is possible to provide rational dosage regimen guidelines. Population PK/PD is a modelling discipline and we use a variety of Maximum Likelihood and Bayesian techniques to perform the modelling. Current therapeutic applications include malaria, paediatrics, anti-inflammatories and anti-cancer agents.

Computer aided clinical trial design

Computer aided clinical trial design (CATD) builds on population modelling and is a model based technique in which future clinical trials are designed based on the current state of knowledge using stochastic simulation techniques. The work is carried out within CAPKR. The methodology has been applied to an anti-migraine drug.

Optimal design for population PK/PD studies

The use of optimal design techniques is an alternative to CATD and aims to minimise parameter estimation error using various information criteria. Both frequentist and Bayesian methods are being applied. This work is also being carried out in CAPKR and we are currently working on both the methodology and developing software.

Members of the Statistical Modelling Researcher Group:

  • Kayode Ogungbenro
  • Henry Pertinez
  • Eleanor Howgate (Ph.D. student)
  • Sheryl Perry (part time Ph.D. student)

Scientific Research Links:

 

Teaching

  • Foundation Mathematics
  • Pharmaceutical Calculations
  • Pharmacokinetics Drug
  • Development Biopharmaceutics
 

Biography

Professor Leon Aarons is a Professor in the School of Pharmacy and Pharmaceutical Sciences at the University of Manchester, UK.  Following a postdoctoral fellowship at the School of Chemistry, University of Leeds, he came to Manchester in 1976.

His major research interests lie in the area of pharmacokinetics.  He has a general interest in the subject as a whole but has a special interest in data analysis and interpretation.  He collaborates with members of the pharmacokinetic group in Manchester and also with other scientists in industry and academia throughout Europe.  His current activities revolve around population pharmacokinetics.  People involved in the drug development process are becoming increasingly aware of the importance of studying the pharmacokinetic and pharmacodynamics of the drug in the population interest as soon as possible.

He is a member on various committees promoting research including the United Kingdom Pharmacokinetic Discussion Group and is a member of the management committee of COST B25.

He is European Editor of the Journal of Pharmacokinetics and Pharmacodynamics and Executive Editor of the British Journal of Clinical Pharmacology.

 

Qualifications

  • 1973 - PhD (University of Manchester)
  • 1971 - MSc (University of Calgary)
  • 1968 - BSc (Sydney)
 

Collaborators and affiliated staff

  • CAPKR Collaboration: Brian Houston, Aleksandra Galetin, Amin Rostami,  David Hallifax, Jeff Penny
  • Postdoctoral Research Fellow: Kayode Ogungbenro
  • Postdoctoral Research Associate: Henry Pertinez
  • PhD Students: Eleanor Howgate, Sheryl Perry (part-time)
 

Selected publications

2011

  • Guest EJ, Aarons L, Houston JB, Rostami-Hodjegan A, Galetin A. (2011). Critique of the two-fold measure of prediction success for ratios:application for the assessment of drug-drug interactions. Drug Metab Dispos, 39(2), 170-173. eScholarID:95952 | DOI:10.1124/dmd.110.036103
  • I Perogamvros, L Aarons, AG Miller, PJ Trainer and DW Ray. (2011). Corticosteroid-binding globulin regulates cortisol pharmacokinetics. Clinical Endocrinology, 74, 30-36. eScholarID:119107 | DOI:10.1111/j.1365-2265.2010.03897.x
  • Kayode Ogungbenro, Lakshmi Vasist, Robert Maclaren, George Dukes, Malcolm Young and Leon Aarons. (2011). A semi-mechanistic gastric emptying model for the population pharmacokinetic analysis of orall administered acetaminophen in critically ill patients. Pharm Res, 28, 394-404. eScholarID:112723 | DOI:10.1007/s11095-010-0290-8

2010

  • Eunice Yuen, Ivelina Gueorguieva, Stephen Wise, Danny Soon, Leon Aarons. (2010). Ethnic differences in the population pharmacokinetics and pharmacodynamics of warfarin. J Pharmacokinet Pharmacodyn, 37, 3-24. eScholarID:84355 | DOI:10.1007/s10928-009-9138-4
  • K Ogungbenro, R MacLaren, G Dukes, M Young, L Aarons, LS Vasist. (2010). Population Pharmacokinetic Modeling of Acetaminophen (APAP), A Surrogate for Gastric Emptying, in Critically Ill Patients Tolerant And Intolerant To Enteral Nutrition. Clinical Pharmacology and Therapeutics, 87, S1-S7. eScholarID:83406
  • K.Ogungbenro, L.Aarons. (2010). Sample Size/Power Calculations for Repeated Ordinal Measurements in Population Pharmacodynamic Experiments. Journal of Pharmacokinetic and Pharmacodynamics, 37(1), 67-83. eScholarID:83408 | DOI:10.1007/s10928-009-9144-6
  • L.Aarons and K.Ogungbenro. (2010). Optimal Design of Pharmacokinetic Studies. Basic & Clinical Pharmacology & Toxicology, 106, 250-255. eScholarID:83411 | DOI:10.1111/j.1742-7843.2009.00533.x

2009

  • Dokoumetzidis A, Aarons L. (2009). Proper lumping in systems biology models. IET Systems Biology, 3, 40-51. eScholarID:1d18756 | DOI:10.1049/iet-syb:20070055
  • Emma Dean, Duncan Jodrell, Kate Connolly, Sarah Dobson, Jacques Jolivet, Jon Durkin, Stephen Morris, Debra Jowle, Tim Ward, Jeff Cummings, Gemma Dickinson, Aarons, L, Eric LaCasse, Lesley Robson, Dive, C, Malcolm Ranson. (2009). Phase I trial of AEG35156 Administered as a 7-day and 3-day continuous intravenous infusion in patients with advanced refractory cancer. Journal of Clinical Oncology, 27, 1-9. eScholarID:1d18768 | DOI:10.1200/JCO.2008.19.5677
  • K.Ogungbenro, A.Dokoumetzidis, L.Aarons. (2009). Application of Optimal Design Methodologies in Clinical Pharmacology Experiments. Pharmaceutical Statistics, 8(3), 239-252. eScholarID:83414 | DOI:10.1002/pst.354
  • K.Ogungbenro, I.Matthews, M.Looby, G.Kaiser, G.Graham, L.Aarons. (2009). Population Pharmacokinetics and Optimal Design of Paediatric Studies for Famciclovir. British Journal of Clinical Pharmacology, 68(4), 546-560. eScholarID:83413 | DOI:10.1111/j.1365-2125.2009.03479.x
  • Kayode Ogungbenro, Leon Aarons. (2009). An effective approach for obtaining optimal sampling windows for population pharmacokinetic experiments. Journal of Biopharm Statistics, 19, 174-189. eScholarID:43603 | DOI:10.1080/10543400802536131

2008

  • Aristides Dokoumetzidis, Leon Aarons. (2008). Analytical expressions for combining population pharmacokinetic parameters from different studies. Journal of Biopharm Statis, 18, 662-676. eScholarID:43224 | DOI:10.1080/10543400802071360
  • Kayode Ogungbenro, Leon Aarons. (2008). How many subjects are necessary for population pharmacokinetic experiments? Confidence interval approach. Eur J Clin Pharmacol, 64, 705-713. eScholarID:43722 | DOI:10.1007/s00228-008-0493-7
  • Kayode Ogungbenro, Leon Aarons. (2008). Optimisation of sampling windows design for population pharmacokinetic experiments. J Pharmacokinet Pharmacodyn, 35, 465-482. eScholarID:43380 | DOI:10.1007/s10928-008-9097-1
  • Marylore Chenel, Francois Bouzom, Aarons L, Ogungbenro K. (2008). Drug-drug interaction predictions with PBPK models and optimal multiresponse sampling time designs: application to midazolam and a phase I compound. Part 1: comparison of uniresponse and multiresponse design using PopDes. J Pharmacokinet Pharmacodyn, 35, 635-659. eScholarID:1d18457 | DOI:10.1007/s10928-008-9104-6
  • Marylore Chenel, Francois Bouzom, Fanny Cazade, Ogungbenro K, Aarons L, France Mentre. (2008). Drug-drug interaction predictions with PBPK models and optimal multiresponse sampling time designs: application to midazolam as a phase 1 compound. Part 2: clinial trial results. J Pharmacokinet Pharmacodyn, 35, 661-681. eScholarID:1d18459 | DOI:10.1007/s10928-008-9105-5
  • Ogungbenro K, Aarons L. (2008). Sample size calculations for population pharmacodynamic experiments involving repeated dichotomous observations. J of Biopharm Statistics, 18, eScholarID:1d18460 | DOI:10.1080/105400802375845
  • Ogungbenro K, Gordon Graham, Ivelina Gueorguieva, Aarons L. (2008). Incorporating correlation in interindividual variability for the optimal design of multiresponse pharmacokinetic experiments. Journal of Biopharmaceutical Statistics, 18, 342-358. eScholarID:1d17042 | DOI:10.1080/10543400701697208

2007

  • Grant Langdon, Ivelina Gueorguieva, Aarons L, Mats Karlsson. (2007). Linking preclinical and clinical whole-body physiologically based pharmacokinetic models with prior distributions in NONMEM. Eur J Clin Pharmacol, 63, 485-498. eScholarID:1d16091

2006

  • Dokoumetzidis A, Aarons L. (2006). Propagation of Population PK and PD Information using a Bayesian Approach: Dealing with Non-Exchangeability. Journal of Pharmacokinetics and Pharmacodynamics, 33, 29-48. eScholarID:1d13418
  • Geraint R Davies, Richard Brindle, Saye H Khoo, Aarons L. (2006). Use of nonlinear mixed-effects analysis for improved precision of early pharmacodynamic measures in tuberculosis treatment. Antimicrobial Agents and Chemotherapy, 50(9), 3154-3156. eScholarID:1d13651 | DOI:10.1128/AAC.00774-05

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