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

  • Nerea Ferreirós
  • Sebastian Dresen
  • Maren Hermanns-Clausen
  • Volker Auwaerter
  • Annette Thierauf
  • Christoph Müller
  • Roland Hentschel
  • Rainer Trittler
  • Gisela Skopp
  • Wolfgang WeinmannEmail author
Original Article

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.

Keywords

Fatal codeine intoxication Dosing errors Extensive metabolizer Long-release medication 

Notes

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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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Nerea Ferreirós
    • 1
  • Sebastian Dresen
    • 1
  • Maren Hermanns-Clausen
    • 2
  • Volker Auwaerter
    • 1
  • Annette Thierauf
    • 1
  • Christoph Müller
    • 3
  • Roland Hentschel
    • 3
  • Rainer Trittler
    • 4
  • Gisela Skopp
    • 5
  • Wolfgang Weinmann
    • 1
    • 6
    Email author
  1. 1.Institute of Forensic MedicineFreiburg University Medical CenterFreiburgGermany
  2. 2.Poisons Information Center VIZ-FreiburgCenter for Pediatrics and Adolescent MedicineFreiburgGermany
  3. 3.Center for Pediatrics and Adolescent MedicineFreiburg University Medical CenterFreiburgGermany
  4. 4.Pharmacy of Freiburg University Medical CenterFreiburgGermany
  5. 5.Institute of Legal and Traffic MedicineUniversity HospitalHeidelbergGermany
  6. 6.Institute of Forensic Medicine, Forensic ToxicologyUniversity HospitalFreiburgGermany

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