1 / 21

Presented by Terry Blaschke, M.D. at the meeting of the Clinical Pharmacology Subcommittee

Presented by Terry Blaschke, M.D. at the meeting of the Clinical Pharmacology Subcommittee of the Advisory Committee for Pharmaceutical Science. Computers and Biomedical Research 1972;5:441-59. Ann Intern Med 1975;82:619-27. J Pharmacokinet Biopharm 1980;8:553-71. .

bernie
Download Presentation

Presented by Terry Blaschke, M.D. at the meeting of the Clinical Pharmacology Subcommittee

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Presented by Terry Blaschke, M.D. at the meeting of the Clinical Pharmacology Subcommittee of the Advisory Committee for Pharmaceutical Science

  2. Computers and Biomedical Research 1972;5:441-59

  3. Ann Intern Med 1975;82:619-27

  4. J Pharmacokinet Biopharm 1980;8:553-71. Evaluation of methods for estimating population pharmacokinetics parameters. I. Michaelis-Menten model: routine clinical pharmacokinetic data.Sheiner LB, Beal SL.Individual pharmacokinetic par parameters quantify the pharmacokinetics of an individual, while population pharmacokinetic parameters quantify population mean kinetics, interindividual variability, and residual intraindividual variability plus measurement error. Individual pharmacokinetics are estimated by fitting individual data to a pharmacokinetic model. Population pharmacokinetic parameters are estimated either by fitting all individual's data together as though there was no individual kinetic differences (the naive pooled data approach), or by fitting each individual's data separately, and then combining the individual parameter estimates (the two-stage approach). A third approach, NONMEM, takes a middle course between these, and avoids shortcomings of each of them…This performance is exactly what is expected from theoretical considerations and provides empirical support for the use of NONMEM when estimating population pharmacokinetics from routine type patient data.

  5. Clin Pharmacol Ther 1979;25:358-71 Simultaneous modeling of pharmacokinetics and pharmacodynamics: application to d-tubocurarine.Sheiner LB, Stanski DR, Vozeh S, Miller RD, Ham J.We propose a model of drug pharmacodynamic response that when integrated with a pharmacokinetic model allows characterization of the temporal aspects of pharmacodynamics as well as the time-independent sensitivity component. The total model can accommodate extremes of effect. It allows fitting of simultaneous plasma concentration (Cp) and effect data from the initial distribution phase of drug administration, or from any non-equilibrium phase. The model postulates a hypothetical effect compartment, the dynamics of which are adjusted to reflect the temporal dynamics of drug effect.

  6. Three Compartment Model plus an “Effect Site”

  7. Clinical Pharmacokinetics 1981;6:429-53

  8. Clin Pharmacol Ther 1989;46:63-77

  9. Benefit:Risk Response Surface Drug Effects (EFFICACY/TOXICITY) RCT * • Patient • Characteristics • age • kidney function • severity of illness * Drug Regimens EXPOSURE INPUT PROFILE (Courtesy of Lewis Sheiner)

  10. Br J Clin Pharmacol, 2000;54:203–11

  11. Annu Rev Pharmacol Toxicol 2000;40:67-95

  12. FDA SERVICE & ADVISORY BOARDS - • 1987- Expert Consultant to the FDA; Center FOR Drug Evaluation and Research (formerly Center for Drugs and Biologics), Rockville, MD • 1991-94 Member, Antiviral Drugs Advisory Committee, CDER, FDA, Rockville, MD • 1997 Member, Expert panel: Guidance on Population PK/PD, CDER, FDA, Rockville, MD. • 1998- Member, Expert Panel: Individual and Population Bioequivalence, CDER, FDA, Rockville, MD • 1999- Member, Expert Panel: Exposure-Response Guidance, CDER, FDA, Rockville, MD • 2002- Member, Clinical Pharmacology Subcommittee

  13. VISITING FACULTY SUPERVISED: Brian Whiting, MD Adrian Dunne, PhD (with SL Beal) Robert Laplanche, PhD Margaret Lynn McFayden, PhD Pascal Girard, PhD Margareta Hammarlund-Udenaes, PhD Xiaojaian Zhou, PhD Jeffrey Koup, PhD

  14. POST DOCTORAL SCHOLARS SUPERVISED: Carl Peck, MD Diana Nicoll, MD, PhD Hillel Halkin, MD Samuel Vozeh, MD Renato Galeazzi, MD Donald Stanski, MD Peter Ravenscroft, MD David Wicker, MD Nestor Sanchez, MD Thaddeus Grasela, PharmD Eliane Fuseau, PhD Johan Gabrielson, PhD Nicholas Holford, MSc, MB, CHB Jashvant Unadkat, PhD Lawrence Wheeler, MD, PhD Stanley Perkins, MD Herve Porchet, MD Nancy Sambol, PharmD Ferenc Bartha Davide Verotta, PhD Yukiya Hashimoto, PhD Beny Mozes, MD Shi Jun, MD Ruediger Port, MD Dominik Uehlinger, MD Leslie Lenert, MD (Stanford) Kazumasa Aizawa, PhD Inaki Fernandez-Toconiz, PhD Mats Karlsson, PhD Karen Fattinger-Bachmann, MD Jacob Mandema, PhD Janet Wade, PhD (with N. Sambol) Kyungsoo Park, PhD Jean-Michel Gries, PhD Atsunori Kaibara, PhD Saraswati Kinkare, PhD Christine Veyrat, PhD Eugene Cox, PhD Yoshitaka Yano, PhD Ikuko Yano, PhD (with S. Beal) Niclas Jonsson, PhD Jianfeng Lu, PhD Marc Pfister, MD Line Labbe, PhD Dolors Soy, PhD Micha Levy, PhD

More Related