Universität zu Köln

Fuhr, Uwe, Hsin, Chih-hsuan, Li, Xia, Jabrane, Wafaa and Soergel, Fritz (2019). Assessment of Pharmacokinetic Drug-Drug Interactions in Humans: In Vivo Probe Substrates for Drug Metabolism and Drug Transport Revisited. In: Annual Review of Pharmacology and Toxicology, S. 507 - 537. PALO ALTO: ANNUAL REVIEWS. ISBN 978-0-8243-0459-1

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Abstract

Pharmacokinetic parameters of selective probe substrates are used to quantify the activity of an individual pharmacokinetic process (PKP) and the effect of perpetrator drugs thereon in clinical drug-drug interaction (DDI) studies. For instance, oral caffeine is used to quantify hepatic CYP1A2 activity, and oral dagibatran etexilate for intestinal P-glycoprotein (P-gp) activity. However, no probe substrate depends exclusively on the PKP it is meant to quantify. Lack of selectivity for a given enzyme/transporter and expression of the respective enzyme/transporter at several sites in the human body are the main challenges. Thus, a detailed understanding of the role of individual PKPs for the pharmacokinetics of any probe substrate is essential to allocate the effect of a perpetrator drug to a specific PKP; this is a prerequisite for reliably informed pharmacokinetic models that will allow for the quantitative prediction of perpetrator effects on therapeutic drugs, also in respective patient populations not included in DDI studies.

Item Type:	Book Section, Proceedings Item or annotation in a legal commentary
Creators:	Creators Email ORCID ORCID Put Code Fuhr, Uwe UNSPECIFIED UNSPECIFIED UNSPECIFIED Hsin, Chih-hsuan UNSPECIFIED UNSPECIFIED UNSPECIFIED Li, Xia UNSPECIFIED UNSPECIFIED UNSPECIFIED Jabrane, Wafaa UNSPECIFIED UNSPECIFIED UNSPECIFIED Soergel, Fritz UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-140032
DOI:	10.1146/annurev-pharmtox-010818-021909
Title of Book:	Annual Review of Pharmacology and Toxicology
Series Name:	Annu. Rev. Pharmacol. Toxicol.
Volume:	59
Page Range:	S. 507 - 537
Date:	2019
Publisher:	ANNUAL REVIEWS
Place of Publication:	PALO ALTO
ISSN:	0362-1642
ISBN:	978-0-8243-0459-1
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ORGANIC ANION TRANSPORTER-2; LIVER BLOOD-FLOW; P-GLYCOPROTEIN; CYTOCHROME-P450 3A; RENAL CLEARANCE; HEPATIC DRUG; S-WARFARIN; CLINICAL PHARMACOKINETICS; QUANTITATIVE PREDICTION; COCKTAIL INTERACTION Multiple languages Pharmacology & Pharmacy; Toxicology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/14003