Universität zu Köln

Iwersen-Bergmann, S., Plattner, S., Hischke, S., Mueller, A., Andresen-Streichert, H., Jungen, H., Erb, R. and Beer-Sandner, B. (2021). Brain/blood ratios of methadone and ABCB1 polymorphisms in methadone-related deaths. Int. J. Legal Med., 135 (2). S. 473 - 483. NEW YORK: SPRINGER. ISSN 1437-1596

Full text not available from this repository.

Abstract

Methadone is an opioid that often leads to fatalities. Interpretation of toxicological findings can be challenging if no further information about the case history is available. The aims of this study were (1) to determine whether brain/blood ratios can assist in the interpretation of methadone findings in fatalities; (2) to examine whether polymorphisms in the gene encoding the P-glycoprotein (also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1)), which functions as a multispecific efflux pump in the blood-brain barrier, affect brain/blood ratios of methadone. Femoral venous blood and brain tissue (medulla oblongata and cerebellum) from 107 methadone-related deaths were analysed for methadone by gas chromatography-mass spectrometry. In addition, all the samples were genotyped for three common ABCB1 single nucleotide polymorphisms (SNPs rs1045642, rs1128503, and rs2032582) using ion-pair reversed-phase high-performance liquid chromatography-electrospray ionization mass spectrometry (ICEMS). In nearly all cases, methadone concentrations were higher in the brain than in the blood. Inter-individual brain/blood ratios varied (0.6-11.6); the mean ratio was 2.85 (standard deviation 1.83, median 2.35). Moreover, significant differences in mean brain/blood ratios were detected among the synonymous genotypes of rs1045642 in ABCB1 (p = 0.001). Cases with the T/T genotype had significantly higher brain/blood ratios than cases with the other genotypes (T/T vs. T/C difference (d) = 1.54, 95% CI [1.14, 2.05], p = 0.002; T/T vs. C/C d = 1.60, 95% CI [1.13, 2.29], p = 0.004). Our results suggest that the rs1045642 polymorphisms in ABCB1 may affect methadone concentrations in the brain and its site of action and may be an additional factor influencing methadone toxicity.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Iwersen-Bergmann, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Plattner, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hischke, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Andresen-Streichert, H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Jungen, H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Erb, R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Beer-Sandner, B. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-582170
DOI:	10.1007/s00414-021-02502-5
Journal or Publication Title:	Int. J. Legal Med.
Volume:	135
Number:	2
Page Range:	S. 473 - 483
Date:	2021
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1437-1596
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language Medicine, Legal Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58217