Oxycodone findings and CYP2D6 function in postmortem cases

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Oxycodone findings and CYP2D6 function in postmortem cases

Jakobsson, Gerd (författare): Linköpings universitet,Avdelningen för klinisk kemi och farmakologi,Medicinska fakulteten,Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Artillerigatan 12, S-58758 Linkoping, Sweden

Larsson, Ronja (författare): Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Artillerigatan 12, S-58758 Linkoping, Sweden

Pelle, Lucia (författare): Linköpings universitet,Avdelningen för läkemedelsforskning,Medicinska fakulteten

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Kronstrand, Robert (författare): Linköpings universitet,Avdelningen för klinisk kemi och farmakologi,Medicinska fakulteten,Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Artillerigatan 12, S-58758 Linkoping, Sweden

Green, Henrik (författare): Linköpings universitet,Avdelningen för klinisk kemi och farmakologi,Medicinska fakulteten,Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Artillerigatan 12, S-58758 Linkoping, Sweden

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ELSEVIER IRELAND LTD, 2021
2021
Engelska.
Ingår i: Forensic Science International. - : ELSEVIER IRELAND LTD. - 1872-4973 .- 1878-0326. ; 53

Relaterad länk:: http://www.fsigeneti...; visa fler...; https://urn.kb.se/re...; https://doi.org/10.1...; visa färre...

Tidskriftsartikel (refereegranskat)

Abstract Ämnesord

Stäng

Genetic disposition can cause variation in oxycodone pharmacokinetic characteristics and decrease or increase the expected clinical response. In forensic medicine, determination of cause of death or assessing time between drug intake and death can be facilitated by knowledge of parent and metabolite concentrations. In this study, the aim was to investigate if CYP2D6 genotyping can facilitate interpretation by investigating the frequency of the four CYP2D6 phenotypes, poor metabolizer, intermediate metabolizer, extensive metabolizer, and ultra-rapid metabolizer in postmortem cases, and to study if the CYP2D6 activity was associated with a certain cause of death, concentration, or metabolic ratio. Cases positive for oxycodone in femoral blood (n = 174) were genotyped by pyrosequencing for CYP2D6*3, *4, and *6 and concentrations of oxycodone, noroxycodone, oxymorphone, and noroxymorphone were determined by LC-MS/MS (LLOQ 0.005 mu g/g). Digital droplet PCR was used to determine the copy number variation for CYP2D6*5. Cases were categorized by cause of death. It was found that poor and intermediate CYP2D6 metabolizers had significantly higher oxycodone and noroxycodone concentrations compared to extensive and ultra-rapid metabolizers. CYP2D6 phenotype were equally distributed between cause of death groups, showing that no phenotype was overrepresented in any of the cause of death groups. We also found that the concentration ratio between oxymorphone and oxycodone depended on the CYP2D6 activity when death was unrelated to intoxication. In general, a low metabolite to parent ratio indicate an acute intake. By using receiver operating characteristic (ROC) analysis, we conclude that an oxymorphone/ oxycodone ratio lower than 0.075 has a high sensitivity for separating intoxications with oxycodone from other intoxications and non-intoxications. However, the phenotype needs to be known to reach a high specificity. Therefore, the ratio should not be used as a biomarker on its own to distinguish between different causes of death but needs to be complemented by genotyping.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)

Nyckelord

Oxycodone related deaths; Pharmacogenetics; Postmortem toxicology; Metabolite ratios; Forensic Toxicology

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Av författaren/redakt...: Jakobsson, Gerd; Larsson, Ronja; Pelle, Lucia; Kronstrand, Robe ...; Green, Henrik

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Medicinsk geneti ...

Artiklar i publikationen: Forensic Science ...

Av lärosätet: Linköpings universitet

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