Public Defence: Cecilie Hasselø Thaulow - Toxicology

Cand.med. Cecilie Hasselø Thaulow at Institute of Clinical Medicine will be defending the thesis "Metabolites of heroin in post-mortem samples: The pharmacokinetic interaction with ethanol and measurements in several different matrices" for the degree of PhD.

Time and place: Feb. 19, 2019 1:15 PM, Gamle festsal, Domus Academica (Urbygningen), Karl Johans gate 47

Adjudication committee

First opponent: Professor Henrik Druid, Karolinska University Hospital, Department of Oncology- Pathology, Sweden

Second opponent: Professor Ola Dale, NTNU – Norwegian University of Science and Technology

Third member and Chair of the adjudication committee: Associate Professor Marianne Klemp, Faculty of Medicine, University of Oslo

Chair of the Defence

Pro-Dean for Research Jens-Petter Berg, Faculty of Medicine, University of Oslo

Principal Supervisor

Researcher Vigdis Vindenes, Faculty of Medicine, University of Oslo

Summary

Heroin-related deaths are frequently dealt with in forensic medicine, and the toxicological interpretation of such deaths can be challenging. Although ethanol is often detected, the interactions between ethanol and heroin are not completely understood. Toxicological analyses are routinely performed in peripheral blood, but in some autopsies blood is not available due to e.g. decomposition or severe injuries.

This thesis aimed to investigate if there is a pharmacokinetic interaction between ethanol and the metabolism of heroin, and also if measurements of heroin metabolites in several alternative post-mortem matrices other than peripheral blood can be useful in the toxicological assessment of heroin-related deaths. The included studies were based on toxicological analyses performed in post-mortem cases.

The findings indicate that ethanol inhibits two steps in the metabolism of heroin; the hydrolysis of the first heroin metabolite, 6-acetylmorphine (6-AM), to morphine, and the glucuronidation of morphine. Such a pharmacokinetic interaction may complicate the combined use of heroin and ethanol more than what is expected from the pharmacodynamic interaction alone.

In most cases, the morphine concentrations measured in cardiac blood, pericardial fluid, and psoas and lateral vastus muscle were comparable with concentrations in peripheral blood. In addition, roughly the same differences between rapid and delayed deaths in several alternative matrices, as previously described in peripheral blood, were found. Analyses in alternative matrices were also useful in differentiating between intake of heroin and codeine in many cases.

The findings can contribute to better understanding and improved interpretation of toxicological findings in heroin-related deaths. Still, as divergent results were found in some cases throughout the studies, the evaluation of toxicological findings should always be performed with great caution.