Blood methadone concentrations in living and deceased persons: variations over time, subject demographics, and relevance of coingested drugs.

Concentrations of d,l-methadone were determined in blood samples from people arrested for driving under the influence of drugs (DUID), users of illicit drugs, and methadone-related deaths. In drug overdose deaths (N = 346), mean (median) and highest concentrations of methadone in femoral blood were 0.53 mg/L (0.40 mg/L) and 6.7 mg/L, compared with 0.46 mg/L (0.30 mg/L) and 3.7 mg/L in non-poisoning deaths (N = 157) (p < 0.05). In DUID suspects and users of illicit drugs (N = 909), the blood-methadone concentrations were much lower, 0.23 mg/L (0.20 mg/L) and 1.1 mg/L (p < 0.001). The median concentration of methadone in blood decreased as the number of coingested drugs increased in the overdose deaths: 0.5 mg/L with methadone the only drug compared with 0.2 mg/L with 6-9 other drugs present (p < 0.001). These coingested drugs were mainly benzodiazepines (diazepam, alprazolam, flunitrazepam) and amphetamines; THC and morphine (from heroin) were the major illicit drugs. The overlap in blood-methadone concentrations in living cases and autopsy cases makes it difficult to conclude that methadone overdose was the cause of death. Adverse drug-drug interactions and varying degrees of tolerance to opiates complicate the interpretation.