Titre du document / Document title

Oxycodone involvement in drug abuse deaths. II. Evidence for toxic multiple drug-drug interactions

Auteur(s) / Author(s)

CONE Edward J. ⁽¹⁾ ; FANT Reginald V. ⁽¹⁾ ; ROHAY Jeffrey M. ⁽²⁾ ; CAPLAN Yale H. ⁽³⁾ ; BALLINA Mayra ⁽⁴⁾ ; REDER Robert F. ⁽⁴⁾ ; HADDOX J. David ⁽⁴⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Pinney Associates, Bethesda, Maryland, ETATS-UNIS
⁽²⁾ Pinney Associates, Pittsburgh, Pennsylvania, ETATS-UNIS
⁽³⁾ National Scientific Services, Baltimore, Maryland, ETATS-UNIS
⁽⁴⁾ Purdue Pharma L.P., Stamford, Connecticut, ETATS-UNIS

Résumé / Abstract

Recent surveys suggest that the abuse of drugs, often in combination, is pervasive throughout society. Adverse consequences of drug abuse tend to be attributed to the single drug most likely to be responsible. This is frequently seen in fatality cases, particularly those involving opioids. However, it is difficult to determine the specific cause of death when multiple drugs are involved. Although enhanced toxicity of alcohol and other centrally acting drugs with opioids has been well established in animal studies, there is a paucity of data in well-controlled human studies. We evaluated 1014 fatality cases involving oxycodone (OXC) for evidence of enhanced toxicity associated with multiple drug-drug interactions. We previously reported on these cases, and we classified them by a standardized method into groups that distinguished cases unrelated to drug abuse from those related to drug abuse, cases that involved only OXC from cases involving multiple drugs, drug-induced fatalities from drug-related fatalities, and cases in which the specific drug product OxyContin® (oxycodone HCI controlled-release) tablets were identified from cases where OxyContin was not identified. Our working hypothesis was that OXC in combination with other centrally acting drugs is more toxic than OXC alone, evidenced by the finding of lower mean blood concentrations of OXC in multiple drug-induced deaths compared to single (OXC only) drug-induced deaths. Assessment of blood levels determined by specific assay methodology (primarily gas chromatography-mass spectrometry) in these cases provided the following mean postmortem concentrations of OXC: multiple drug-induced deaths, OxyContin identified, 0.93 mg/mL (N = 167); multiple drug-induced deaths, OxyContin not identified, 0.73 mg/mL (N = 579); single (OXC) drug-induced deaths, OxyContin identified, 1.55 mg/mL (N = 12); and single (OXC) drug-induced deaths, OxyContin not identified, 1.70 mg/mL (N = 15). Overall, mean OXC concentration trends were as follows: single (OXC), drug-induced, drug abuse deaths > multiple, drug-induced drug abuse deaths > drug-related drug abuse deaths deaths unrelated to drug abuse; and deaths in which OxyContin was identified deaths in which OxyContin was not identified, whether the deaths involved oxycodone alone or multiple drugs. Drug abuse patterns in the multiple drug-induced cases were complex. Over 135 drugs that were considered to be plausibly contributory to enhanced toxicity were identified in body fluids and tissues. Evaluation of mean OXC blood concentrations in cases that contained one, two, three, four, five, and six or more contributory drugs in combination demonstrated consistently lower mean OXC concentrations than those cases in which OXC was the only drug identified. A smaller number of cases were evaluated in the multiple drug-induced groups in which OXC was paired with a single other contributory drug. The overall mean OXC concentration for these cases was 0.71 mg/mL (N = 90) as compared to 1.64 mg/mL (N = 27) for the cases in the single drug-induced groups. The consistent finding of lower mean OXC blood levels associated with multiple drug-induced fatalities supports the stated hypothesis that OXC in combination with other centrally active drugs is more toxic than when OXC was the only drug involved. It was concluded that in cases of multiple drug fatalities, cause of death (COD) should not be attributed to any single drug.

Revue / Journal Title

Journal of analytical toxicology   ISSN 0146-4760   CODEN JATOD3 

Source / Source

2004, vol. 28, n^o4, pp. 217-225 [9 page(s) (article)] (29 ref.)

Langue / Language

Anglais

Editeur / Publisher

Preston, Niles, IL, ETATS-UNIS  (1977) (Revue)

Mots-clés anglais / English Keywords

Toxicological exploration ; Forensic aspect ; Autopsy material ; Postmortem ; Blood ; Biological fluid ; Drug of abuse ; Opiates ; Narcotic analgesic ; Oxycodone ; Drug intoxication ; Drug combination ; Drug interaction ;

Mots-clés français / French Keywords

Exploration toxicologique ; Aspect médicolégal ; Matériel autopsie ; Postmortem ; Sang ; Liquide biologique ; Substance toxicomanogène ; Opiacés ; Analgésique narcotique ; Oxycodone ; Intoxication médicamenteuse ; Association médicamenteuse ; Interaction médicamenteuse ;

Mots-clés espagnols / Spanish Keywords

Análisis toxicológico ; Aspecto forense ; Material autopsia ; Postmortem ; Sangre ; Líquido biológico ; Sustancia toxicomanógena ; Opiados ; Analgésico narcotico ; Oxicodona ; Intoxicación medicamentosa ; Asociación medicamentosa ; Interacción medicamentosa ;

Localisation / Location

INIST-CNRS, Cote INIST : 17415, 35400011161354.0010