Subkutane Applikation von Apomorphin - Pharmakologische Eigenschaften und alternative Applikationswege

Zusammenfassung

Apomorphin ist ein Non-Ergot-Aporphinalkaloid vom Dibenzochinolintyp und wirkt als potenter Dopaminagonist. Der schnelle hepatische Metabolismus („First-pass-Effekt”) von Apomorphin macht die orale Applikation unmöglich, sodass die subkutane Injektion in der Therapie des Morbus Parkinson favorisiert wird. Weiterhin sind auch die intranasale, sublinguale, rektale und intravenöse Gabe in der Behandlung des Morbus Parkinson getestet worden. Bei subkutaner Applikation ist die maximale Plasmakonzentration im Mittel nach 10 - 20 Minuten erreicht (T_max), die klinische Wirkung tritt zwischen 7 - 17 Minuten ein. Apomorphin wird im Wesentlichen über nicht enzymatische Oxidation abgebaut, daneben findet die N-Methylierung, Sulfatierung, Glukuronidierung und Catechol-O-Methylierung von Apomorphin statt. In dieser Übersicht werden die pharmakologischen Eigenschaften von subkutan injiziertem Apomorphin detailliert geschildert und die alternativen Applikationswege diskutiert.

Abstract

Apomorphine is a non-ergot aporphine alkaloid with a dibenzoquinoline structure and acts as a potent dopamine agonist. The high hepatic first-pass metabolism of apomorphine prevents its use by the oral route, but the subcutaneous injection is the usual route in the treatment of Parkinson's disease. Furthermore, the intranasal, sublingual, rectal and intravenous application has been investigated in Parkinson's disease. After subcutaneous application the maximal plasma concentration occurs after 10 to 20 minutes (T_max), and the clinical effects start after 7 to 17 minutes. Apomorphin is metabolized mainly by non-enzymatic oxidation, but enzymatic pathways including N-methylation, sulfation, glucuronidation, and catechol-O-methylation are also detected. In the present review we summarize the pharmacological properties of subcutaneously administered apomorphin and discuss the alternative application routes.

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