# Presentation: 725376

## 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 1972;5:441-59

***Computers and Biomedical Research***** 1972;5:441-59**

## Ann Intern Med 1975;82:619-27

## 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.

***J Pharmacokinet Biopharm***** 1980;8:553-71. **

## Clin Pharmacol Ther 1979;25:358-71 

***Clin Pharmacol Ther***** 1979;25:358-71 **

## Three Compartment Model plus an “Effect Site”

## Clinical Pharmacokinetics 1981;6:429-53

***Clinical Pharmacokinetics***** 1981;6:429-53**

## Clin Pharmacol Ther 1989;46:63-77

***Clin Pharmacol Ther***** 1989;46:63-77**

## Benefit:Risk Response Surface

- Drug Regimens
*EXPOSURE*
*INPUT PROFILE*

- Drug Effects
*(EFFICACY/TOXICITY)*

-     Patient
- Characteristics
*age*
*kidney function*
*severity of illness*

- (Courtesy of Lewis Sheiner)

- *

- *

- RCT

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

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

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## Annu Rev Pharmacol Toxicol 2000;40:67-95

***Annu Rev Pharmacol Toxicol***** 2000;40:67-95**

## 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**

## 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**

## 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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