Biomaterial Database

Impact of pharmacokinetic-pharmacodynamic modelling in early clinical drug development. 2017

Jasper Dingemanse, and Andreas Krause

Department of Clinical Pharmacology, Actelion Pharmaceuticals Ltd, Gewerbestrasse 16, 4123 Allschwil, Switzerland. Electronic address: jasper.dingemanse@actelion.com.

Early clinical pharmacology studies in healthy subjects are often dissociated from patient studies. In this review we encourage the use of modelling and simulation techniques to generate valuable information at an early stage of clinical development. We illustrate these principles by presenting 5 different case studies from a spectrum of therapeutic drug classes. Their application leads to a better understanding of drug characteristics early on, thereby facilitating the design of dose-finding studies in the target patient population and saving resources.

UI	MeSH Term	Description	Entries
D008954	Models, Biological	Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.	Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D010599	Pharmacokinetics	Dynamic and kinetic mechanisms of exogenous chemical DRUG LIBERATION; ABSORPTION; BIOLOGICAL TRANSPORT; TISSUE DISTRIBUTION; BIOTRANSFORMATION; elimination; and DRUG TOXICITY as a function of dosage, and rate of METABOLISM. LADMER, ADME and ADMET are abbreviations for liberation, absorption, distribution, metabolism, elimination, and toxicology.	ADME,ADME-Tox,ADMET,Absorption, Distribution, Metabolism, Elimination, and Toxicology,Absorption, Distribution, Metabolism, and Elimination,Drug Kinetics,Kinetics, Drug,LADMER,Liberation, Absorption, Distribution, Metabolism, Elimination, and Response
D010601	Pharmacology, Clinical	The branch of pharmacology that deals directly with the effectiveness and safety of drugs in humans.	Clinical Pharmacology
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D055808	Drug Discovery	The process of finding chemicals for potential therapeutic use.	Drug Prospecting,Discovery, Drug,Prospecting, Drug
D064368	Healthy Volunteers	Persons with no known significant health problems who are recruited to participate in research to test a new drug, device, or intervention as controls for a patient group. (from http://clinicalcenter.nih.gov/recruit/volunteers.html, accessed 2/14/2013)	Healthy Participants,Healthy Subjects,Human Volunteers,Normal Volunteers,Healthy Participant,Healthy Subject,Healthy Volunteer,Human Volunteer,Normal Volunteer,Participant, Healthy,Participants, Healthy,Subject, Healthy,Subjects, Healthy,Volunteer, Healthy,Volunteer, Human,Volunteer, Normal,Volunteers, Human,Volunteers, Normal