|SOFT - TIAFT 1998||Scientific Session 1||Wednesday October 7, 1998|
|THE ROLE OF ETHANOL IN THE ETIOLOGY OF HEROIN-RELATED DEATHS. EVIDENCE FOR PHARMACOKINETIC INTERACTIONS BETWEEN HEROIN AND ALCOHOL|
|Aldo Polettini, Angelo Groppi, and Maria Montagna|
Department of Legal Medicine and Public Health, University of Pavia, Via Forlanini, 12, 27100 PAVIA, Italy
|In order to evaluate the significance of pharmacokinetic interactions between heroin and alcohol in the etiology of heroin related deaths (HRD), the blood concentrations of ethanol (BAC), of free morphine (FM) and of total morphine (TM), as well as the total morphine concentrations in urine and bile were examined in a population of 39 lethal cases. The cases were included in the records of the Department of Legal Medicine and Public Health, University of Pavia in the period January 1997 - April 1998. Morphine was determined using the DPC Coat-A-Count radioimmunoassay with or without enzymatic hydrolysis. The cause of death was attributed to either heroin or associated heroin-ethanol intoxication. Cases were arbitrarily divided in two groups according to BAC (<1000 mg/l, LE, and >1000 mg/l, HE). The differences in the FM and TM concentrations in blood, bile, and urine, and in the FM/TM ratios between the two groups were statistically evaluated (Mann-Whitney U test).
A similar statistical evaluation was carried out on the data published by Goldberger et al. (J. Anal. Toxicol., 18, 1994, 22-28) who studied the disposition of heroin and its metabolites (6-acetylmorphine, free morphine) in blood and urine in 23 lethal cases attributed to either heroin or heroin and alcohol intoxication. In this case the following variables in the LE and HE groups were compared: FM, TM, 6-acetyl-morphine concentration in blood (A), the FM/(FM+A) ratio, the FM/TM ratio, the urinary concentration of heroin (UH), 6-acetylmorphine (UA) and free morphine (UFM), and the UFM/(UFM+UH+UA) ratio.
Statistical analyses of data indicated that high BAC inhibits the hydrolysis of 6-acetymorphine to morphine (FM/(FM+A), p = 0.0025) and that the percentage of inhibition is correlated to BAC (r = 0.67). High BAC was also found to significantly decrease glucuronidation (FM/TM, p = 0.0129), and the excretion of free and conjugated heroin metabolites. According to these results, we advance the hypothesis that pharmacokinetic interactions between heroin and ethanol do occur in the organism of individuals exposed to high doses of these substances.