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Chronische PDE-5-Hemmung bei erektiler Dysfunktion

Neuer Therapieansatz mit täglicher Einmalgabe von Tadalafil

Chronic PDE-5 inhibition in patients with erectile dysfunction

New treatment approach using once daily Tadalafil

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Zusammenfassung

Patienten mit erektiler Dysfunktion (ED) haben häufig auch ein erhöhtes kardiovaskuläres Risiko. Eine Schädigung des Gefäßendothels (endotheliale Dysfunktion) mit herabgesetzter Stickoxidsynthase- (NOS-)Aktivität und hierdurch verminderter Bioverfügbarkeit von Stickoxid (NO) scheint das pathogenetische Bindeglied zwischen ED und Herz-Kreislauf-Erkrankungen zu sein. Die zentrale Bedeutung des NO-Guanylatzyklase-cGMP-Mechanismus für den Erektionsvorgang spiegelt sich in der therapeutischen Wirksamkeit von Hemmstoffen der Phosphodiesterase-5 (PDE-5) bei der ED wider. Im Gegensatz zu anderen derzeit verfügbaren PDE-5-Hemmern mit Halbwertszeiten von ca. 4 h führt die lange Halbwertszeit von Tadalafil mit 17,5 h zu einer klinischen Wirksamkeit von bis zu 36 h, sodass eine Einzeldosis Tadalafil während dieses Zeitraums die Erektion verbessern kann. Die umfangreichsten klinischen Erfahrungen mit PDE-5-Hemmern liegen bislang mit einer bedarfsabhängigen Medikation vor, doch haben inzwischen mehrere Studien gezeigt, dass Tadalafil auch in niedrigen Dosierungen bei regelmäßiger, einmal täglicher Verabreichung sehr gut wirksam und verträglich ist. In 3 randomisierten, placebokontrollierten doppelblinden Multicenterstudien ließ sich anhand unterschiedlicher validierter Messparameter der erektilen Funktion belegen, dass Tadalafil in täglichen Dosen von 2,5, 5 oder 10 mg Placebo signifikant überlegen ist. In einer weiteren Studie war Tadalafil einmal täglich auch noch nach Versagen einer bedarfsgeleiteten Therapie wirksam.

In einer kontrollierten Cross-over-Studie gaben 72% der Patienten der täglichen Tadalafil-Therapie den Vorzug gegenüber einer bedarfsabhängigen Applikation, wobei hierfür insbesondere eine bessere sowie längere Wirksamkeit von Tadalafil mit der Ermöglichung eines wieder weitgehend spontanen Sexuallebens angegeben wurde. Eine Pilotstudie zeigte zudem, dass die regelmäßige Tadalafil-Einnahme im Gegensatz zur Bedarfsmedikation verschiedene Marker der Endothelfunktion an Penis- und anderen Gefäßen verbesserte.

Abstract

Erectile dysfunction (ED) is often associated with increased cardiovascular risk. There is increasing evidence suggesting that dysfunction of the vascular endothelium with reduced bioavailability of nitric oxide (NO) may be the pathogenetic link between ED and cardiovascular disease. The crucial importance of the NO-guanylatecyclase-cGMP-phosphodiesterase pathway for penile erection is mirrored by the efficacy of phosphodiesterase-5 (PDE5) inhibitors in the treatment of ED. In contrast to other currently available PDE5 inhibitors with a half-life time of about 4 h Tadalafil has a half-life time of about 17.5 h resulting in erectile responsiveness for up to 36 h after 1 single dose. Most clinical experience has been reported with on-demand use of PDE-5 inhibitors, but meanwhile several studies were able to demonstrate that Tadalafil given daily in low (2.5 and 5 mg) doses is both highly effective and well-tolerated. In three randomized, double-blind, placebo-controlled multi-center trials, various validated measures of erectile function indicated that once daily Tadalafil at doses of 2.5, 5, and 10 mg was significantly superior to placebo.

In another mono-center trial, once daily Tadalafil has shown significant efficacy even after failure of on-demand treatment. In a controlled cross-over study of on-demand versus daily Tadalafil treatment, 72% of the patients preferred once daily administration, mainly because of superior and longer efficacy allowing a more spontaneous sexual life. Interestingly in a pilot study of on-demand versus chronic administration of Tadalafil for 4 weeks, only regular dosing improved several markers of endothelial function.

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Interessenkonflikt

Der korrespondierende Autor weist auf folgende Beziehungen hin: Berater und Investigator für Lilly, Bayer, Pfizer und Janssen-Cilag. Trotz des möglichen Interessenkonflikts ist der Beitrag unabhängig und produktneutral.

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  1. Praxis für Urologie und Andrologie, Neuer Jungfernstieg 6a, 20354, Hamburg, Deutschland

    H. Porst

  2. Medizinische Abteilung, Lilly Deutschland GmbH, Bad Homburg, Deutschland

    K. Hell-Momeni & H. Büttner

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Porst, H., Hell-Momeni, K. & Büttner, H. Chronische PDE-5-Hemmung bei erektiler Dysfunktion. Urologe 48, 1318–1329 (2009). https://doi.org/10.1007/s00120-009-2089-y

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