Fatal and severe codeine intoxication in 3-year-old twins--interpretation of drug and metabolite concentrations.
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.
Institute of Forensic Medicine, Freiburg University Medical Center, Freiburg, Germany.
Nerea
N
Ferreirós
Sebastian
S
Dresen
Maren
M
Hermanns-Clausen
Volker
V
Auwaerter
Annette
A
Thierauf
Christoph
C
Müller
Roland
R
Hentschel
Rainer
R
Trittler
Gisela
G
Skopp
Wolfgang
W
Weinmann
D000996:Antitussive Agents / Q000032:analysis / Q000493:pharmacokinetics* / Q000506:poisoning*; D001923:Brain Chemistry; D001929:Brain Edema / Q000473:pathology; D002675:Child, Preschool; D002853:Chromatography, Liquid; D003061:Codeine / Q000031:analogs & derivatives / Q000032:analysis / Q000493:pharmacokinetics* / Q000506:poisoning*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D003692:Delayed-Action Preparations; D062787:Drug Overdose; D017809:Fatal Outcome; D053593:Forensic Toxicology; D005838:Genotype; D020719:Glucuronides / Q000032:analysis; D006801:Humans; D008508:Medication Errors; D009020:Morphine / Q000032:analysis; D009022:Morphine Derivatives / Q000032:analysis; D011110:Polymorphism, Genetic; D053120:Respiratory Aspiration / Q000473:pathology; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution; D014430:Twins, Monozygotic
D000996:Antitussive Agents; D003692:Delayed-Action Preparations; D020719:Glucuronides; D009022:Morphine Derivatives; C010414:norcodeine; C035349:morphine-6-glucuronide; D009020:Morphine; D019389:Cytochrome P-450 CYP2D6; C018108:morphine-3-glucuronide; D003061:Codeine; C010616:normorphine