Abstract
Propoxyphene and its major metabolite norpropoxyphene have been determined in blood and liver in 29 cases of death in which propoxyphene, either as the hydrochloride or as the napsylate salt, was involved. The use of propoxyphene napsylate (Darvon-N) contributed to the deaths of 4 persons, 3 of whom were former heroin addicts receiving large amounts of this drug in connection with propoxyphene substitution programs. In the majority of cases the norpropoxyphene blood concentrations exceed the propoxyphene concentrations, although brain determinations in several instances indicate that norpropoxyphene does not cross the blood-brain barrier with the same ease as propoxyphene. On the basis of the comparative toxicities of propoxyphene and norpropoxyphene in animals and the high tissue concentrations of norpropoxyphene in man after propoxyphene administration, it is conceivable that norpropoxyphene contributes to the toxic effects of propoxyphene.
Zusammenfassung
Im Blut und Lebergewebe von 29 tödlich verlaufenen Vergiftungsfällen mit Propoxyphen (entweder als Hydrochlorid oder als Napsylat = Salz der β-Naphthylsulfonsäure) wurde Propoxyphen und sein Hauptmetabolit Norpropoxyphen bestimmt. Die Anwendung von Propoxyphen-Napsylat führte bei 4 Patienten zum Tode, 3 von ihnen erhielten große Mengen der Substanz im Rahmen einer Erhaltungstherapie nach Heroin-Abhängigkeit. Bei der Mehrzahl der untersuchten Fälle war die gefundene Konzentration von Norpropoxyphen im Blut höher als die von Propoxyphen. Die Messung der Hirnkonzentrationen in einigen Fällen deutet darauf hin, daß Norpropoxyphen nicht mit gleicher Geschwindigkeit wie Propoxyphen die Blut-Hirn-Schranke zu durchschreiten vermag. Unter Berücksichtigung der Toxicitäten von Propoxyphen und Norpropoxyphen bei Tieren und den gefundenen hohen Norpropoxyphen-Konzentrationen nach Vergiftung mit Propoxyphen erscheint es denkbar, daß dem Metaboliten Norpropoxyphen eine Bedeutung für die toxischen Wirkungen von Propoxyphen zukommt.
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Baselt, R.C., Wright, J.A., Turner, J.E. et al. Propoxyphene and norpropoxyphene tissue concentrations in fatalities associated with propoxyphene hydrochloride and propoxyphene napsylate. Arch. Toxicol. 34, 145–152 (1975). https://doi.org/10.1007/BF00353315
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DOI: https://doi.org/10.1007/BF00353315