- 期刊
Effect of Ketoconazole Treatment on Cortisol Response under Adrenocorticotropin Hormone Stimulation in Dogs
Ketoconazole於犬隻血清氫基皮質酮生合成對親腎上腺皮質激素刺激反應之作用
摘要
Ketoconazole (KCZ)為臨床上imidazole類衍生物之抗黴菌劑，亦為類固醇荷爾蒙生合成之抑制劑。本研究之目的在於瞭解不同劑量之KCZ對犬隻腎上腺氫基皮質酮生成及對親腎上腺皮質激素刺激反應之影響。以高劑量(30 mg/kg of body weight)及低劑量(10 mg/kg of body weight)之KCZ分別投予各六隻對親腎上腺皮質激素刺激正常反應之犬隻，之後再以0.25 mg合成的親腎上腺皮質激素(Cortrosyn^®)肌肉注射犬隻，而分別於KCZ投藥前、投藥後四小時及親腎上腺皮質激素注射後二及四小時抽血分離血清檢體。以ELISA組(NEOGEN^®)檢測氫基皮質酮血清濃度。KCZ可顯著地抑制氫基皮質酮的分泌(P＜0.005)，尤其是高劑量組；另外，KCZ亦可使犬隻對親腎上腺皮質激素刺激反應顯著地降低(P＜0.05)，尤其是高劑量組。至於在時間方面，親腎上腺皮質激素刺激後四小時的氫基皮質酮上升的數值比二小時後為高(P＜0.05)。結果顯示KCZ的劑量及時間上對親腎上腺皮質激素刺激反應之抑制具有顯著的差異性。
並列摘要
Ketoconazole (KCZ), a clinically used imidazole antifungal agent, also inhibits steroid hormones biosynthesis. This study investigated how different dosages of KCZ affect cortisol secretion of adrenal glands and its response towards adrenocorticotropin hormone (ACTH) stimulation in dogs. Two groups of 6 healthy dogs were orally administered with a low dose (10 mg/kg of body weight) and a high dose (30 mg/kg of body weight) of KCZ, respectively. Synthetic ACTH (Cortrosyn^®) of 0.25 mg was continuously administered by IM to each dog. Blood samples were collected from each dog before and 4 hours after KCZ administration, and then 2 hours and 4 hours after ACTH injection to determine the level of serum cortisol. Serum concentrations of cortisol were measured using ELISA kit (NEOGEN^®). KCZ, particularly the high dose group, significantly inhibited the secretion of cortisol (P＜0.005) and decreased the response to ACTH stimulation (P＜0.05). However, the increased serum cortisol level at 4 hours after ACTH stimulation was higher than at 2 hours after ACTH stimulation (P＜0.05). The experimental results indicated how dosage and time appear to affect KCZ treatment on cortisol response to ACTH stimulation in dogs.