Downregulation von LH bei der Hündin nach Anwendung des GnRH-Agonisten Buserelin in Implantatform

Zusammenfassung

Gegenstand und Ziel: Darstellung der Downregulation von LH bei der Hündin nach Anwendung eines Slow-Release-GnRH-Implantats mit dem Wirkstoff Buserelin. Material und Methoden: Zur Ausschaltung negativ rückkoppelnder Wirkungen endogener Sexualhormone wurden neun Hündinnen ovariohysterektomiert. Zur Anwendung kam der Wirkstoff Buserelinacetat in Form des Slow-Release-Implantats Profact Depot^®, wobei jeweils drei Hündinnen Implantate mit 3,3 mg, 6,6 mg oder 13,2 mg subkutan appliziert wurden. Die Charakterisierung der Verfügbarkeit von LH erfolgte durch punktuelle sowie durch sequenzielle Blutentnahmen über 6-stündige Zeitfenster. Folgende Parameter wurden erfasst: AUC (Area Under the Curve), Basalkonzentration, Anzahl der Pulse und maximale Pulsamplitude. Ergebnisse: Dosisabhängigkeiten waren nicht feststellbar, was darauf hindeutet, dass die niedrigste Dosis bereits maximal wirksam war. Für die weitere Auswertung wurden die Tiere daher zu einer Gruppe zusammengefasst. Ein zunehmend stärker werdender Effekt der Downregulation zeigte sich von der 2. bis zur 26. Woche nach der Implantation, die Wirkdauer lag bei ca. 34 Wochen. Eine Stunde nach der Implantation kam es zu einem signifikanten Anstieg auf fast das Doppelte des Ausgangswerts. Danach blieb das LH-Niveau über weitere 8 Stunden erhöht. Schlussfolgerung: Wie beim Rüden führt Buserelin auch bei der Hündin zu einer Downregulation der LH-Sekretion, der eine initiale, über mehrere Stunden anhaltende erhöhte LH-Freisetzung vorausgeht. Diese muss im Zusammenhang mit den unerwünschten Wirkungen gesehen werden, die bei der Downregulation der Ovarfunktion der Hündin mittels Slow-Release-GnRH-Analoga auftreten. Klinische Relevanz: Die Unterbindung des initialen Anstiegs der LH-Konzentration ist Voraussetzung für eine erfolgreiche Anwendung von Slow-Release-GnRH-Analoga zur Downregulation der Sexualfunktion der Hündin.

Summary

Objectives: Demonstration of downregulation of luteinizing hormone (LH) using the gonadotropin-releasing hormone (GnRH)-agonist buserelin as the active ingredient in the form of a slow-release implant. Material and methods: To eliminate any negative feedback mechanisms of endogenous sex steroids, nine bitches were ovariohysterectomized prior to treatment. The applied drug was the slow-release implant Profact Depot^® with the active ingredient buserelin; dosages were 3.3, 6.6 or 13.2 mg per dog (n = 3 per group). LH bioavailability was assessed in single blood samples and in sequential blood samples collected over a 6-hour time windows, which allowed determination of the AUC (area under the curve), basal concentration, number of pulses and maximal pulse-amplitude. Results: No dose dependency was observed, leading to the conclusion that maximum efficiency could already be achieved using the lowest dose of 3.3 mg. Therefore, for further evaluation, the dogs were combined as a single group. An increasing downregulatory effect was observed from weeks 2 to 26, with the pharmacodynamic activity lasting approximately 34 weeks. There was a significant increase 1 hour after implantation to almost twice the pre-treatment value; elevated but continuously declining LH concentrations lasted a further 8 hours. Conclusion: Similar as in male dogs, in the bitch buserelin in the form of a slow-release implant also led to downregulation of LH secretion with a preceding initial increase lasting for several hours. This increase must be seen in relation to the unwanted side effects when using this type of drug for downregulation of ovarian function in the bitch. Clinical relevance: Inhibition of the initial LH increase appears to be an important factor to allow for routine clinical use of slow-release GnRH-agonist implants in the bitch.

Schlüsselwörter

Kastration - Feedback - Wirkdauer - Nebenwirkungen

Keywords

Castration - feedback - efficacy - side effects

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