Terry Blaschke, M.D.

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Presented by Terry Blaschke, M.D. at the meeting
of the Clinical Pharmacology Subcommittee of the
Advisory Committee for Pharmaceutical Science
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Computers and Biomedical Research 19725441-59
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Ann Intern Med 197582619-27
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J Pharmacokinet Biopharm 19808553-71.
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
themThis 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.
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Clin Pharmacol Ther 197925358-71
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.
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Three Compartment Model plus an Effect Site
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Clinical Pharmacokinetics 19816429-53
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Clin Pharmacol Ther 19894663-77
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BenefitRisk Response Surface
Drug Effects (EFFICACY/TOXICITY)
RCT

Patient Characteristics age kidney
function severity of illness

Drug Regimens EXPOSURE INPUT PROFILE
(Courtesy of Lewis Sheiner)
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Br J Clin Pharmacol, 20005420311
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Annu Rev Pharmacol Toxicol 20004067-95
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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

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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
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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
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