Documentation concerning the metabolism of cinnarizine is requested.

Fråga: Documentation concerning the metabolism of cinnarizine is requested.

Sammanfattning: In vitro studies have shown that CYP1A2, CYP2B6, CYP2C9 and CYP2D6 are involved in the metabolism of cinnarazine. It is not possible at present to evaluate the clinical implications of these data since in vivo data is lacking.

Svar: Cinnarizine is a piperazine derivate with histamine H1-receptor and calcium channel blocking activity (1). It is used for symptomatic treatment of nausea and vertigo in Sweden (2).

Cinnarizine is extensively metabolised in the liver and is excreted in the faeces mainly as unchanged drug and in the urine predominantly as metabolite (1).

In vitro studies performed indicate that CYP1A2, CYP2B6, CYP2C9 and CYP2D6 are involved in the metabolism of cinnarazine (3,4) and that CYP2D6 seems to be the most important enzyme involved (4). It is, however, not possible to evaluate the clinical implications of these findings since in vivo data is lacking. 1 Martindale, The extra pharmacopoeia, 1996; 31st ed: 2 The Swedish catalogue of approved medical products 3 Narimatsu S, Kariya S, Isozaki S, Ohmori S, Kitada M, Hosokawa S, Msubuchi Y, Suzuki T: Involvement of CYP2D6 in oxidative metabolism of cinnarizine and flunarizine in human liver microsomes. Biochem Biophys Res Commun 1993; 193: 1262-1268 4 Kariya S, Isozaki S, Uchino K, Suzuki T, Narimatsu S: Oxidative metabolism of flunarizine and cinnarizine by microsomes from B-lymphoblasoid cell lines expressing human cytochrome P450 enzymes. Biol Pharm Bull 1996; 19: 1511-1514