Profile: Jeffrey S. Barrett, Ph.D., FCP

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Director, Laboratory for Applied PK/PD
Research Associate Professor, Department of Pediatrics
Email: barrettj@email.chop.edu
Phone: 267-426-5479

Research Interests

Dr. Barrett was recruited to the division in 2003 to create a pharmacometric modeling and simulation center of excellence. His industrial experience in various clinical pharmacology settings provides a unique perspective to the division. Dr. Barrett is Research Associate Professor of Pediatrics and Director of the Laboratory for Applied PK/PD within The Division of Clinical Pharmacology and Therapeutics. He has served as the Laboratory Core Director for the CHOP Pediatric Pharmacology Research Unit from 2003-2005 and has assumed the role of Principal Investigator from Dr. Adamson in 2006. He received his B.S. from Drexel University in Chemical Engineering and his Ph.D. in Pharmaceutics from the University of Michigan. Prior to joining CHOP, Dr. Barrett spent 13 years in the pharmaceutical industry involved primarily with clinical PK/PD aspects of clinical drug development. Dr. Barrett has co-authored over 55 manuscripts and has given over 40 invited lectures on a variety of topics related to clinical drug development. He was elected to Fellow of the American College of Clinical Pharmacology (ACCP) in 2000 and was awarded the Tanabe Young Investigator Award in 2002. Dr. Barrett is the Chair for Clinical Sciences/AAPS and a Regent of the ACCP. He was elected as a Fellow of AAPS in 2004 and currently serves on the Clinical Pharmacology Advisory Committee to the US Food and Drug Administration.

Dr. Barrett's research is focused on investigating sources of variation in PK/PD with modeling and simulation strategies to develop rational dosing guidance for targeted (e.g. pediatric) populations. Clinical trial simulation is utilized prospectively to explore design dependencies and parameter sensitivities. Dr. Barrett also focuses on the development of pharmacometric approaches to advance PK-PD, novel biomarker development and disease progression modeling. His desire to return to academia was in part to better train the next generation of pediatric clinical pharmacologists in population modeling methodologies.

Education and Training

INSTITUTION AND LOCATION DEGREE YEAR(s) FIELD OF STUDY
Drexel University , Philadelphia , PA BS 1981-1986 Chemical Engineering
University of Michigan , Ann Arbor , MI MS 1986-1987 Pharmacokinetics
University of Michigan , Ann Arbor , MI PhD 1987-1990 Pharmacokinetics
University of Michigan , Ann Arbor , MI   1988-1990 Biostatistics

 

1990-94 Merck Research Laboratories, West Point PA : Senior Research Pharmacokineticist
1994-96 Somerset Pharmaceuticals, Tampa , FL : Director, Computer Resources and Pharmacokinetics
1994-97 U. South Florida School of Medicine, Department of Pharmacology, Adjunct Clinical Assistant Professor
1996-01 DuPont Pharmaceuticals, Newark , DE , Director, Clinical Pharmacokinetics
1997- University of Florida School of Pharmacy, Department of Pharmaceutics, Adjunct Professor
2001-03 Aventis Pharmaceuticals, Bridgewater , NJ , Global Head, Clinical Biopharmaceutics
2003- Children's Hospital of Philadelphia , Philadelphia , PA , Research Associate Professor, Clinical Pharmacology

 

1998-00 Chair, Delaware Valley Drug Metabolism Discussion Group
1998-00 FDA Expert Panel Member on Individual and Population Bioequivalence (Blue-Ribbon Panel)
1999 PhRMA Committee Award for Leadership, Expert Panel on Individual and Population Bioequivalence
1999 Elected Fellow, American College of Clinical Pharmacology
1999- Advisory Board, East Coast Population Approach Users Group
2002- National Advisory Board, University of Florida College of Pharmacy
2002-2003 Program Committee, Annual Meeting of American College of Clinical Pharmacology
2002 Tanabe Young Investigator Award, American College of Clinical Pharmacology
2004 Elected Fellow, American Association of Pharmaceutical Science
2004- FDA Clinical Pharmacology Advisory Board
2005 Elected member, Children's Oncology Group

 

  1. Meibohm B, Panetta C, Barrett JS . Population pharmacokinetic studies in pediatrics: Issues in design and analysis. AAPS Journal .  7(2): Article 48: E475-E487, 2005 .
  2. Kenna LA, Labbe L, Barrett JS , Pfister M. Modeling and simulation of adherence: Approaches and applications in Therapeutics. AAPS Journal .  7(2): E390-E407, 2005.
  3. Zuppa AF , Mondick J, Davis LA, Maka D, Tsang B, Narayan M, Nicholson C, Patel D, Collison KR, Adamson PC, Barrett JS . Drug Utilization in the Pediatric Intensive Care Unit: Monitoring Prescribing Trends and Establishing Prioritization of Pharmacotherapeutic Evaluation of Critically-ill Children. J. Clin. Pharmacol. 45: 1305-1312, 2005.
  4. Barrett JS , Labbe L, Pfister M. Application and impact of population pharmacokinetics in the assessment of antiretroviral pharmacotherapy. Clinical Pharmacokinetics 44(6): 591-625, 2005.
  5. Pfister M, Martin NE, Haskell LP, Barrett JS . Optimizing dose selection with modeling and simulation: application to the vasopeptidase inhibitor M100240. J. Clin Pharmacol 44(6): 621-631, 2004.
  6. Zuppa AF, Adamson PC, Barrett JS . Letter to the Editor, Pediatric drug labeling: improving the safety and efficacy of pediatric therapies, J Pediatr. Pharmacol Ther 9(1): 70-71, 2004.
  7.  Barrett JS and Collison KR. Dosing LMWHs in Special Populations: Safety, PK/PD and Monitoring Considerations. Int. J. Cardiovascular Medicine and Science 4(2): 41-54, 2004.
  8. Mousa, SA, Bozarth J, Johansen, K, and Barrett, JS. Tinzaparin molecular weight distributions are potent stimulants for sustained release of plasma tissue factor pathway inhibitor in healthy human subjects. J. Clin. Pharmacol. 43(7): 727-734, 2003.
  9. Hainer JW, Barrett JS , Assaid C, Fossler M, Cox D, Leathers T, Leese P. Dosing in heavy-weight/obese patients with the LMWH, tinzaparin: A pharmacodynamic study. Thromb. Haemost . 87: 817-23, 2002.
  10. Koprowski SP and Barrett JS Data warehouse implementation with clinical pharmacokinetic/pharmacodynamic data. Int. J. Clin. Pharmacol. Ther . 40 (Suppl 1): S14-S29, 2002.
  11. Barrett JS and Koprowski SP. The epiphany of data warehousing in the pharmaceutical industry. Int. J. Clin. Pharmacol. Ther . 40 (Suppl 1): S3-S13, 2002.
  12. Barrett JS , Joshi AS , Chai M, Ludden TM, Fiske WD and Pieniaszek Jr. HJ. Population pharmacokinetic meta-analysis with efavirenz. Int. J. Clin. Pharmacol. Ther . 40(11): 507-519, 2002 .
  13. Barrett JS, Kornhauser DH, Hainer JW, Gaskill J, Hua TA, Strogel P, Johansen K, van Lier JJ, Knebel W, Pieniaszek HJ. Anticoagulant pharmacodynamics of tinzaparin following 175 IU/kg subcutaneous administration to healthy volunteers. Thrombosis Res. 101: 243-254, 2001 .
  14. Fossler MJ, Barrett JS , Hainer JW, Riddle JG, Ostergaard P, van der Elst E, Sprogel P. P harmacodynamics of intravenous and subcutaneous tinzaparin and heparin in healthy volunteers. American J. Health-Syst Pharm. 58: 1614-21, 2001.
  15. Barrett JS , Gibiansky E, Hull RD , Planès A, Pentikis H, Hainer JW, Hua TA, Gastonguay M. Population pharmacodynamics in patients receiving tinzaparin for the prevention and treatment of deep vein thrombosis. Int. J. Clin. Pharmacol. Ther. 39(10): 431-446, 2001 .
  16. Greenberg HE, Wissel P, Barrett J , Barchowsky A, Gould R Farrell D, Panebianco D, Hand E, Gillen L, Goldberg MR and Bjornsson TD. Antiplatelet effects of MK-852, a platelet fibrinogen receptor antagonist, in healthy volunteers. J. Clin. Pharmacol. 40: 496-507, 2000.
  17. Barrett JS , Yu J, Kapil R, Padovani P, Brown F, Ebling WF, Corjay MH, Reilly TM, Bozarth JM, Mousa SA and Pieniaszek Jr HJ. Disposition and exposure of the fibrinogen receptor antagonist XV459 on a IIB b 3 binding sites in the guinea pig. Biopharm. Drug Disposit . 20(6): 309-318, 1999.
  18. Barrett JS , Hochadel TJ, Morales RJ, Rohatagi S, DeWitt KE, Watson SK, Darnow J, Azzaro A, and DiSanto AR. Tyramine pressor response following single 24-hr application of a selegiline transdermal system (STS) in healthy males. J. Clin. Pharmacol. 37: 238-247, 1997.
  19. Rohatagi S and Barrett JS. Integrated pharmacokinetic modeling of ipriflavone and metabolites after oral administration. Am. J. Ther. 4: 189-198, 1997.
  20. Rohatagi S, Barrett JS , McDonald LJ, Morris EM, Darnow J, and DiSanto AR. Selegiline percutaneous absorption in various species and metabolism by human skin. Pharmaceutical Research 14(1): 50-55, 1997 .
  21. Barrett JS , Wahl RL, and Fisher SJ. Postural effects on peritoneal transport and systemic uptake of radiolabeled monoclonal antibodies. Cancer Immunology and Immunotherapy , 44: 173-178, 1997.
  22. Chen S, Kumar S, Barrett JS , and Wedlund P. A genetic bias in clinical trials?: Cytochrome P450-2D6 (CYP2D6) genotype in general vs selected healthy subject populations. Br. J. Clin. Pharmacol . 44: 303-305, 1997.
  23. Rohatagi S, Barrett JS , DeWitt KE, and Morales RM. Integrated pharmacokinetic modeling of selegiline and metabolites after transdermal delivery. Biopharm. Drug Disposit . 18(7): 567-584, 1997.
  24. Barrett JS , DiSanto AR , Thomford PJ, Larsen EM, Palazzolo MJ, and Morales RM. Toxicokinetic Evaluation of a Selegiline Transdermal System (STS) in the Dog. Biopharm. Drug Disposit. 18(2): 165-184, 1997.
  25. Barrett JS , Szego P, Rohatagi S, Morales RM, DeWitt KE, Rajewski G, and Ireland J. Absorption and presystemic metabolism of selegiline hydrochloride at different regions in the gastrointestinal tract in healthy males. Pharm. Research 13(10): 1533-1538, 1996.
  26. Barrett JS , Murphy MG, Peerlink K, De Lepeleire I, Gould RJ, Panebianco D, Hand E, Deckmyn H, Vermylen J, Arnout J. Pharmacokinetics and pharmacodynamics of MK-383, a selective non-peptide platelet GP IIb/IIIa receptor anatgonist, in healthy men. Clin. Pharmacol. Ther. 56: 377-388, 1994 .
  27. Vielhaber JP, Barrett JS. NM-Win: A pc-based MS windows front-end to NONMEM. Pharmaceutical Research 11(5): 709-713, 1994.
  28. Barrett JS , Gould RJ, Ellis JD, Holahan MM, Stranieri MT, Lynch JJ, Hartman GD, Ihle N, Duggan M, Moreno O, and Theoharides AD. Pharmacokinetics and pharmacodynamics of L-703,014, a potent fibrinogen receptor antagonist, after intravenous and oral administration in the dog. Pharm. Research 11(3): 426-431, 1994 .

 

NIH U01, HD037255-06 (PI: Barrett JS) 1/1/04 – 12/31/09
NIH / NICHD, Pediatric Pharmacology Research Unit
The major goals of this project are to facilitate and promote pediatric labeling of new drugs or drugs already on the market. The overall goal of the PPRU Network is the safe and effective use of drugs in children. The PPRU Network (1) conducts studies on the pharmacokinetics and pharmacodynamics of drugs in children, (2) provides a locus for pre- and post-marketing clinical trials in children conducted by pediatric clinical pharmacologists in collaboration with the pharmaceutical industry and contract research organizations, and (3) serves as an advisory body to the pharmaceutical industry, regulatory agencies, health professionals and the public on the appropriate use of drugs in children. Solvay Inc. (PI: Mascarenhas) 12/01/04 -- 5/30/06

Malabsorption Blood Test: A Novel Approach to Quantify Steatorrhea
The goals of the project is to develop a malabsorption blood test, using two odd chained fatty acids, that will replace the 72-hour stool collection as a more acceptable, accurate and precise assessment of fat malabsorption in subjects with pancreatic insufficiency (including CF). Modeling and simulation techniques are utilized to define the conditions of the test and partition sources of variation among patient subpopulations in support of product labeling.

NIH U01, CA098543-02S1 (PI: Reaman) 10/1/04 – 9/30/07
NIH / NCI, Actinomycin-D/Vincristine Exposure-response in children with cancer
The project pursues the clinical investigation of actinomycin-D and vincristine in children with cancer as a subcontract to the Children's Oncology Group (COG) award. The project goals include a data mining effort to establish relationships between exposure and clinical outcomes in children diagnosed with Wilm's tumor or rhabdomyosarcoma, the establishment of a procedure to both dose and draw blood for drug assay from a single central venous catheter, population-based pharmacokinetic modeling effort to define the sources of variation in subpopulations receiving vincristine and actinomycin-D and a prospective clinical trial utilized to (a) refine such a model, (b) explore pharmacogenetic sources of variation, (c) confirm relationships established between exposure and clinical outcomes and (d) derive dosing rules suitable for labeling.

NIH R01 (PI: Schulman) 3/1/05 – 3/1/08
NIH/NIMH, Pediatric Off-Patent Drug Study (PODS) Center- Sodium Nitroprusside
This project involves the design, analysis and conduct of two trials investigating sodium nitroprusside in pediatric patients based on BPCA initiatives for exploring pharmacotherapy of poorly defined agents used extensively in pediatric populations. The specific aims of the first trial are (1) to define the onset and offset of blood pressure lowering effects of nitroprusside in order to obtain adequate instructions for dose titration and (2) to construct a pharmacokinetic/pharmacodynamic model that defines the relationship between nitroprusside infusion rate and changes in blood pressure. This investigation will also focus on the laboratory support of parent sodium nitroprusside and metabolite exposure in various biologic matrices (i.e., plasma and urine) and PK/PD and population-based modeling in support of the study objectives.

NIH P01 MH076388 (PI: Douglas ) 8/1/05 – 7/31/09
NIMH / NAID, Neurokinin1-R antagonists for HIV therapy
The goal of this Integrated Preclinical/Clinical Program (IPCP) is to identify an NK-1R antagonist that is: (a) active as an anti-HIV agent through interaction with chemokine/cytokine receptors ( Project 1 ); (b) is specific for chemokine and G-protein coupled receptors ( Project 2 ); (c) is safe for use in SIV-infected non-human primates and provides proof of concept related to antiviral, immunomodulatory, and neurobehavioral effects ( Project 3 ); and, (d) is safe in humans and has positive immunomodulatory effects ( Project 4 ). All projects contribute to understanding the basic virologic, molecular and cellular immunologic mechanisms of SP, NK-1R antagonists, and HIV/SIV infection.