Universität zu Köln

Machnik, Marc, Kaiser, Simone, Koppe, Sophie, Kietzmann, Manfred, Schenk, Ina, Duee, Michael, Thevis, Mario, Schaenzer, Wilhelm and Toutain, Pierre-Louis (2017). Control of methylxanthines in the competition horse: pharmacokinetic/pharmacodynamic studies on caffeine, theobromine and theophylline for the assessment of irrelevant concentrations. Drug Test. Anal., 9 (9). S. 1372 - 1385. HOBOKEN: WILEY. ISSN 1942-7611

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Abstract

Methylxanthines positives in competition samples have challenged doping control laboratories and racing jurisdictions since methylxanthines are naturally occurring prohibited substances and often constituents of feed. For theobromine, an international threshold (renamed in International Residue Limit, IRL) of 2 mu g/mL in urine has been established. On the basis of the data presented herein, a threshold or rather an IRL for theobromine in plasma of 0.3 mu g/mL was proposed and was thereupon approved by the International Federation of Horseracing Authorities (IFHA). Official recommendations for reporting caffeine and theophylline are still lacking. The aim of the study was to investigate IRLs for theobromine in blood and for caffeine and theophylline in blood and urine. Therefore, a set of six administrations were carried out including both single i.v. and single oral administrations of caffeine, theobromine and theophylline. Plasma and urine concentrations were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS). Applying the Toutain model approach an effective plasma concentration (EPC) of caffeine was estimated at 3.05 mu g/mL, irrelevant concentrations in blood (IPC) and urine (IUC) approached 6 and 12ng/mL, respectively. EPC of theobromine was calculated with 3.80 mu g/mL, and irrelevant concentrations of theobromine were determined at 8ng/mL in plasma and at 142ng/mL in urine. Toutain modelling of the theophylline data produced an EPC, IPC, and IUC of 3.20 mu g/mL, 6ng/mL, and 75ng/mL, respectively. The obtained irrelevant concentrations were used to postulate IRLs for theobromine in plasma and for caffeine and theophylline in plasma and urine. Copyright (C) 2016 John Wiley & Sons, Ltd.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Machnik, Marc UNSPECIFIED UNSPECIFIED UNSPECIFIED Kaiser, Simone UNSPECIFIED UNSPECIFIED UNSPECIFIED Koppe, Sophie UNSPECIFIED UNSPECIFIED UNSPECIFIED Kietzmann, Manfred UNSPECIFIED UNSPECIFIED UNSPECIFIED Schenk, Ina UNSPECIFIED UNSPECIFIED UNSPECIFIED Duee, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Thevis, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED Schaenzer, Wilhelm UNSPECIFIED UNSPECIFIED UNSPECIFIED Toutain, Pierre-Louis UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-218620
DOI:	10.1002/dta.2097
Journal or Publication Title:	Drug Test. Anal.
Volume:	9
Number:	9
Page Range:	S. 1372 - 1385
Date:	2017
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1942-7611
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CENTRAL-NERVOUS-SYSTEM; ADENOSINE RECEPTORS; URINE; PHARMACOKINETICS; CHROMATOGRAPHY; BIOSYNTHESIS; PHARMACOLOGY; METABOLISM; MECHANISMS; EXCRETION Multiple languages Biochemical Research Methods; Chemistry, Analytical; Pharmacology & Pharmacy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/21862