Universität zu Köln

Trueck, Christina, Hsin, Chih-hsuan, Scherf-Clavel, Oliver, Schaeffeler, Elke, Lenssen, Rebekka, Gazzaz, Malaz, Gersie, Marleen, Taubert, Max ORCID: 0000-0001-8925-7782, Quasdorff, Maria, Schwab, Matthias, Kinzig, Martina, Soergel, Fritz, Stoffel, Marc S. and Fuhr, Uwe (2019). A Clinical Drug-Drug Interaction Study Assessing a Novel Drug Transporter Phenotyping Cocktail With Adefovir, Sitagliptin, Metformin, Pitavastatin, and Digoxin. Clin. Pharmacol. Ther., 106 (6). S. 1398 - 1408. HOBOKEN: WILEY. ISSN 1532-6535

Full text not available from this repository.

Abstract

A new probe drug cocktail containing substrates of important drug transporters was tested for mutual interactions in a clinical trial. The cocktail consisted of (predominant transporter; primary phenotyping metric): 10 mg adefovir-dipivoxil (OAT1; renal clearance (CLR)), 100 mg sitagliptin (OAT3; CLR), 500 mg metformin (several renal transporters; CLR), 2 mg pitavastatin (OATP1B1; clearance/F), and 0.5 mg digoxin (intestinal P-gp, renal P-gp, and OATP4C1; peak plasma concentration (C-max) and CLR). Using a randomized six-period, open change-over design, single oral doses were administrated either concomitantly or separately to 24 healthy male and female volunteers. Phenotyping metrics were evaluated by noncompartmental analysis and compared between periods by the standard average bioequivalence approach (boundaries for ratios 0.80-1.25). Primary metrics supported the absence of relevant interactions, whereas secondary metrics suggested that mainly adefovir was a victim of minor drug-drug interactions (DDIs). All drugs were well tolerated. This cocktail may be another useful tool to assess transporter-based DDIs in vivo.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Trueck, Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED Hsin, Chih-hsuan UNSPECIFIED UNSPECIFIED UNSPECIFIED Scherf-Clavel, Oliver UNSPECIFIED UNSPECIFIED UNSPECIFIED Schaeffeler, Elke UNSPECIFIED UNSPECIFIED UNSPECIFIED Lenssen, Rebekka UNSPECIFIED UNSPECIFIED UNSPECIFIED Gazzaz, Malaz UNSPECIFIED UNSPECIFIED UNSPECIFIED Gersie, Marleen UNSPECIFIED UNSPECIFIED UNSPECIFIED Taubert, Max UNSPECIFIED orcid.org/0000-0001-8925-7782 UNSPECIFIED Quasdorff, Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwab, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Kinzig, Martina UNSPECIFIED UNSPECIFIED UNSPECIFIED Soergel, Fritz UNSPECIFIED UNSPECIFIED UNSPECIFIED Stoffel, Marc S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fuhr, Uwe UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-144462
DOI:	10.1002/cpt.1564
Journal or Publication Title:	Clin. Pharmacol. Ther.
Volume:	106
Number:	6
Page Range:	S. 1398 - 1408
Date:	2019
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1532-6535
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INTESTINAL P-GLYCOPROTEIN; PROBE DRUGS; RENAL CLEARANCE; ABCB1 MDR1; PHARMACOKINETICS; FUROSEMIDE; IMPACT; ELIMINATION; INHIBITORS Multiple languages Pharmacology & Pharmacy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/14446