Pharmacokinetic/Pharmacodynamic Modeling in Drug Development
- 1 April 2000
- journal article
- review article
- Published by Annual Reviews in Annual Review of Pharmacology and Toxicology
- Vol. 40 (1), 67-95
- https://doi.org/10.1146/annurev.pharmtox.40.1.67
Abstract
We propose a framework for considering the role of pharmacokinetic/ pharmacodynamic modeling in drug development and an appraisal of its current and potential impact on that activity. After some introduction, definitions, and background information on drug development, we discuss subject-matter models that underlie pharmacokinetic/pharmacodynamic modeling and show how they determine appropriate statistical models. We discuss the broad role modeling can play in drug development, enhancing primarily the “learning” steps, i.e. acquiring the information needed for the label and for planning efficient confirmatory clinical trials. Examples of past applications of modeling to drug development are presented in tabular form, followed by a discussion of some practical issues in application. Modeling will not reach its potential utility until it is manifest as a visible and separate work unit within a drug development program. We suggest that that work unit is the “in numero” study: a protocol-driven exercise designed to extract additional information, and/or answer a specific drug-development question, through an integrated model-based (meta-) analysis of existent raw data, often pooled across separate (clinical) studies.Keywords
This publication has 58 references indexed in Scilit:
- Simulation of Clinical TrialsAnnual Review of Pharmacology and Toxicology, 2000
- Prediction of Hepatic Metabolic Clearance Based on Interspecies Allometric Scaling Techniques and In Vitro-In Vivo CorrelationsClinical Pharmacokinetics, 1999
- An Evaluation of the Integration of Pharmacokinetic and Pharmacodynamic Principles in Clinical Drug DevelopmentClinical Pharmacokinetics, 1997
- Facilitated analysis of data on drug regimen complianceStatistics in Medicine, 1997
- Role of Population Pharmacokinetics in Drug DevelopmentClinical Pharmacokinetics, 1997
- The Use of Population Pharmacokinetics in Drug DevelopmentClinical Pharmacokinetics, 1996
- The Target Concentration Approach to Clinical Drug DevelopmentClinical Pharmacokinetics, 1995
- Pharmacodynamic ModellingClinical Pharmacokinetics, 1991
- Understanding the Dose-Effect RelationshipClinical Pharmacokinetics, 1981
- APriori lithium dosage regimen using population characteristics of pharmacokinetic parametersJournal of Pharmacokinetics and Biopharmaceutics, 1979