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2.
J Forensic Sci ; 55(2): 551-3, 2010 Mar 01.
Article in English | MEDLINE | ID: mdl-20158595

ABSTRACT

Ethylmorphine, an opiate that is partially metabolized to morphine, is a common ingredient in antitussive preparations. We present a case where a 10-month-old boy was administered ethylmorphine in the evening and found dead in bed the following morning. Postmortem toxicological analyses of heart blood by gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry revealed the presence of ethylmorphine and morphine at concentrations of 0.17 muM (0.054 mg/L) and 0.090 muM (0.026 mg/L), respectively. CYP2D6 genotyping showed that the deceased had an extensive metabolizer genotype, signifying a "normal" capacity for metabolizing ethylmorphine to morphine. The autopsy report concluded that death was caused by a combination of opiate-induced sedation and weakening of respiratory drive, a respiratory infection, and a sleeping position that could have impeded breathing. This is the first case report where the death of an infant has been linked to ethylmorphine ingestion.


Subject(s)
Analgesics, Opioid/adverse effects , Ethylmorphine/adverse effects , Airway Obstruction/etiology , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/blood , Cytochrome P-450 CYP2D6/genetics , Ethylmorphine/administration & dosage , Ethylmorphine/blood , Forensic Toxicology , Gas Chromatography-Mass Spectrometry , Genotype , Humans , Infant , Male , Morphine/blood , Posture , Respiration/drug effects , Respiratory Tract Infections/complications , Sleep
4.
Br J Clin Pharmacol ; 39(6): 611-20, 1995 Jun.
Article in English | MEDLINE | ID: mdl-7654478

ABSTRACT

1. The pharmacokinetics of ethylmorphine after administration of a single dose of the cough mixture Cosylan were investigated in 10 healthy subjects. 2. The median urinary recovery of ethylmorphine and measured metabolites was 77% over 48 h. The median tmax of unchanged ethylmorphine was 45 min, and the terminal elimination t1/2 was 2 h. Ethylmorphine-6-glucuronide was found to be the major metabolite. 3. Two subjects had significantly lower urinary recovery (0.48 h) of morphine and morphine-glucuronides than the remainder. Furthermore, these two had urinary metabolic ratios (MRO) and partial metabolic clearances (CLmO) for O-deethylation of ethylmorphine tentatively classifying them phenotypically as poor metabolisers of the debrisoquine/sparteine type. 4. Genotyping for cytochrome P450 (CYP) 2D6 alleles revealed five homozygote (wt/wt) and five heterozygote subjects. Two subjects phenotypically classified as poor metabolisers were genotypically CYP2D6A/wt and CYP2D6D/wt, respectively. 5. Serum and urine samples taken more than 8 and 24 h after administration of ethyl-morphine respectively, contained morphine and morphine-glucuronides, but no ethylmorphine, ethylmorphine-6-glucuronide or (serum only) norethylmorphine. Norethylmorphine could be detected after hydrolysis of urine samples in all subjects. The urinary recovery of the active metabolites morphine and morphine-6-glucuronide after administration of ethylmorphine varied by a factor of 9 between individuals. 6. The wide variation in recovery of morphine and morphine-glucuronides after oral administration of ethylmorphine could not be explained simply by a difference in CYP2D6 genotype. Constitutional variation in other enzymatic pathways involved in ethylmorphine metabolism is probably crucial. Ratios of morphine to parent drug cannot be used to distinguish the source of morphine after administration of ethylmorphine. Norethylmorphine should be included in urine assays for opiates in forensic toxicology, and no firm conclusions about the source of morphine are possible based on serum samples obtained more than 24 h after drug administration.


Subject(s)
Ethylmorphine/pharmacokinetics , Adult , Biotransformation , Cytochrome P-450 Enzyme System/genetics , Cytochrome P-450 Enzyme System/metabolism , Drug Administration Schedule , Ethylmorphine/administration & dosage , Ethylmorphine/adverse effects , Genotype , Glucuronates/metabolism , Humans , Male , Morphine/metabolism
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