Oxycodone Involvement in Drug Abuse Deaths. II. Evidence for Toxic Multiple Drug-Drug Interactions

• Published in: Journal of analytical toxicology 2004-05, Vol.28 (4), p.217-225
• Main Authors: Cone, Edward J., Fant, Reginald V., Rohay, Jeffrey M., Caplan, Yale H., Ballina, Mayra, Reder, Robert F., David Haddox, J.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cause of Death; Drug intoxications. Doping; Drug Synergism; Humans; Medical sciences; Narcotics - blood; Narcotics - poisoning; Oxycodone - blood; Oxycodone - poisoning; Pharmacology. Drug treatments; Substance-Related Disorders - mortality; United States - epidemiology
• ISSN: 0146-4760; 1945-2403
• DOI: 10.1093/jat/28.4.217

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