van Liessum P A, Pieters G F, Smals A G, Hermus A R, Benraad T J, Kloppenborg P W
Department of Medicine, University Hospital Nijmegen, The Netherlands.
Acta Endocrinol (Copenh). 1989 Nov;121(5):714-20. doi: 10.1530/acta.0.1210714.
The recommended dosage schedules for intermittent sc therapy with the somatostatin analogue octreotide in acromegaly vary widely, from 100 to 1500 micrograms daily. As acute administration of octreotide has been shown to predict its long-term response, we performed a single-dose response study in 5 patients with active acromegaly using doses of 25, 50, 100, 200 and 400 micrograms octreotide as well as a placebo injection. Plasma GH of 2 patients did not normalize after any of the injections, but nadir plasma GH overall gradually decreased as doses were increased from 25 to 400 micrograms. The 400 micrograms octreotide dose was superior with regard to the duration of plasma GH suppression to below 5 micrograms/l or 25% of the basal GH level, the mean GH as a percentage of the basal level over the first 4 and 8 h, and the integrated reduction of plasma GH during the first 4 and 8 h. The postprandial integrated insulin secretion during the first 3 h after injection of the octapeptide was significantly lower after 50, 100 and 400 micrograms than after the placebo injection. The mean plasma glucose as a percentage of the basal level during the first 8 h was significantly higher after octreotide after the 200 and 400 micrograms injections. Minor adverse events were seen in 2 patients after injection of 200 and 400 micrograms octreotide. Within the limitations of this single-dose response study it was concluded that injection of 400 micrograms octreotide yields the best results with regard to suppression of GH secretion, whereas the 50, 100 and 200 micrograms doses are superior to 25 micrograms, but do not differ from each other.
生长抑素类似物奥曲肽间歇性皮下注射治疗肢端肥大症的推荐剂量方案差异很大,每日剂量从100微克至1500微克不等。由于已证明奥曲肽的急性给药可预测其长期反应,我们对5例活动期肢端肥大症患者进行了单剂量反应研究,使用25、50、100、200和400微克奥曲肽剂量以及安慰剂注射。2例患者在任何一次注射后血浆生长激素均未恢复正常,但随着剂量从25微克增加到400微克,血浆生长激素的最低点总体上逐渐下降。在将血浆生长激素抑制至低于5微克/升或基础生长激素水平的25%的持续时间、最初4小时和8小时内平均生长激素占基础水平的百分比以及最初4小时和8小时内血浆生长激素的综合降低方面,400微克奥曲肽剂量效果更佳。注射八肽后最初3小时内的餐后胰岛素分泌综合量在注射50、100和400微克后明显低于安慰剂注射后。注射200和400微克奥曲肽后,最初8小时内平均血浆葡萄糖占基础水平的百分比明显高于奥曲肽注射后。2例患者在注射200和400微克奥曲肽后出现轻微不良事件。在这项单剂量反应研究的局限性内,得出的结论是,就生长激素分泌抑制而言,注射400微克奥曲肽产生的效果最佳,而50、100和200微克剂量优于25微克,但彼此之间无差异。