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Buprenorphine-related deaths among drug addicts in France: a report on 20 fatalities
(Mortalités liés à la buprénorphine parmis les usagers de drogues en France : rapport sur 20 cas)
Auteur(s) :
A. TRACQUI ;
P. KINTZ ;
B. LUDES
Article en page(s) :
430-434
Refs biblio. :
36
Domaine :
Drogues illicites / Illicit drugs
Langue(s) :
Français
Thésaurus mots-clés
BUPRENORPHINE
;
MORTALITE
;
TOXICOLOGIE
;
MESURES QUANTITATIVES
Thésaurus géographique
FRANCE
Note générale :
Journal of Analytical Toxicology, 1998, 22, (6), 430-434
Note de contenu :
tabl.
Résumé :
ENGLISH :
This paper reports a series of 20 fatalities involving a high-dose, sublingual buprenorphine (BUP) formulation recently marketed in France for the substitutive therapy of opiate addicts. The files were recorded over a 16-month period from five different urban areas in France. All subjects but one were male, aged 14-18 (mean 26.6). BUP and its primary metabolite norbuprenorphine (norBUP) were assayed in postmortem fluids and viscerae by HPLC-MS. Blood levels for BUP and norBUP ranged from 1.1 to 29.0 ng/mL (mean 8.4 ng/mL) and 0.2 to 12.6 ng/mL (mean 2.6 ng/mL), respectively, that is, within or slightly over the therapeutic range. BUP exhibited extensive tissue distribution, with average postmortem concentrations of 6.0, 35.0, 45.5, and 80.0 ng/g in the myocardium, kidney, brain, and liver, respectively. In blood, as in viscerae, norBUP levels were generally lower than BUP. The highest concentrations were found in the bile for both BUP (range 575-72,650 ng/mL) and norBUP (range 41-30,000 ng/mL). Therefore, bile may represent a sample of choice for postmortem screening. BUP was identified in 9 of the 11 hair samples assayed at concentrations ranging from 6 to 597 ng/g (mean 137 ng/g), whereas norBUP was never detected. Intravenous injection of crushed tablets, a concomitant intake of psychotropics (especially benzodiazepines), and the high dosage of the BUP formulation available in France appear to be the major risk factors for such fatalities. (Review' s abstract)
ENGLISH :
This paper reports a series of 20 fatalities involving a high-dose, sublingual buprenorphine (BUP) formulation recently marketed in France for the substitutive therapy of opiate addicts. The files were recorded over a 16-month period from five different urban areas in France. All subjects but one were male, aged 14-18 (mean 26.6). BUP and its primary metabolite norbuprenorphine (norBUP) were assayed in postmortem fluids and viscerae by HPLC-MS. Blood levels for BUP and norBUP ranged from 1.1 to 29.0 ng/mL (mean 8.4 ng/mL) and 0.2 to 12.6 ng/mL (mean 2.6 ng/mL), respectively, that is, within or slightly over the therapeutic range. BUP exhibited extensive tissue distribution, with average postmortem concentrations of 6.0, 35.0, 45.5, and 80.0 ng/g in the myocardium, kidney, brain, and liver, respectively. In blood, as in viscerae, norBUP levels were generally lower than BUP. The highest concentrations were found in the bile for both BUP (range 575-72,650 ng/mL) and norBUP (range 41-30,000 ng/mL). Therefore, bile may represent a sample of choice for postmortem screening. BUP was identified in 9 of the 11 hair samples assayed at concentrations ranging from 6 to 597 ng/g (mean 137 ng/g), whereas norBUP was never detected. Intravenous injection of crushed tablets, a concomitant intake of psychotropics (especially benzodiazepines), and the high dosage of the BUP formulation available in France appear to be the major risk factors for such fatalities. (Review' s abstract)
Affiliation :
Inst. de Médecine Légale, 11 rue Humann, 67085 Strasbourg
France. France.
France. France.
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