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Fatal and severe codeine intoxication in 3-year-old twins—interpretation of drug and metabolite concentrations

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Abstract

This work presents two cases of codeine intoxication in 3-year-old monozygotic twin brothers while treated with a codeine slow-release formulation. One child had to be admitted to the hospital, whereas the other one died at home after aspiration of gastric content. The concentrations of codeine and major metabolites including morphine and corresponding glucuronide conjugates were measured by liquid chromatography–tandem mass spectrometry in serum, urine, cerebrospinal fluid, and brain tissue, respectively. A genetic polymorphism study was carried out in order to determine the ability of the children to metabolize codeine by O-demethylation. A pharmacokinetic calculation was also performed to estimate the administered dose of codeine in question. High concentrations of all substances were found in samples of both children. The pharmacokinetic estimate suggests an overdose of codeine, and the possible reasons for the high opiate concentrations are discussed. Furthermore, the postmortem distribution—during and after resuscitation—might play a major role in the interpretation of postmortem concentration levels.

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Acknowledgements

The authors thank Dr. Andreas Pahl (Institute of Experimental and Clinical Pharmacology, Erlangen-Nuernberg, Germany) for performing the genotype study, and N. Ferreirós thanks the Basque Government for her postdoctoral grant.

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Authors and Affiliations

  1. Institute of Forensic Medicine, Freiburg University Medical Center, Freiburg, Germany

    Nerea Ferreirós, Sebastian Dresen, Volker Auwaerter, Annette Thierauf & Wolfgang Weinmann

  2. Poisons Information Center VIZ-Freiburg, Center for Pediatrics and Adolescent Medicine, 79106, Freiburg, Germany

    Maren Hermanns-Clausen

  3. Center for Pediatrics and Adolescent Medicine, Freiburg University Medical Center, Freiburg, Germany

    Christoph Müller & Roland Hentschel

  4. Pharmacy of Freiburg University Medical Center, Freiburg, Germany

    Rainer Trittler

  5. Institute of Legal and Traffic Medicine, University Hospital, Heidelberg, Germany

    Gisela Skopp

  6. Institute of Forensic Medicine, Forensic Toxicology, University Hospital, Albertstrasse 9, 79104, Freiburg, Germany

    Wolfgang Weinmann

Authors
  1. Nerea Ferreirós
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  2. Sebastian Dresen
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  3. Maren Hermanns-Clausen
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  4. Volker Auwaerter
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  5. Annette Thierauf
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  6. Christoph Müller
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  7. Roland Hentschel
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  8. Rainer Trittler
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  9. Gisela Skopp
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  10. Wolfgang Weinmann
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Correspondence to Wolfgang Weinmann.

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Ferreirós, N., Dresen, S., Hermanns-Clausen, M. et al. Fatal and severe codeine intoxication in 3-year-old twins—interpretation of drug and metabolite concentrations. Int J Legal Med 123, 387–394 (2009). https://doi.org/10.1007/s00414-009-0340-0

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  • DOI: https://doi.org/10.1007/s00414-009-0340-0

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