Fløgstad A K, Halse J, Haldorsen T, Lancranjan I, Marbach P, Bruns C, Jervell J
Medical Department B, Rikshospitalet, Oslo, Norway.
J Clin Endocrinol Metab. 1995 Dec;80(12):3601-7. doi: 10.1210/jcem.80.12.8530606.
Sandostatin LAR is a sustained release formulation of octreotide that has been developed by microencapsulating the drug with biodegradable poly(lactide-glycolide)-glucose. We have investigated the efficacy and tolerability of Sandostatin LAR given as a single dose im to patients with active acromegaly who showed good GH suppression during a 2- to 4-week pretreatment period with octreotide given sc. Two double blind studies were performed. Initially, 14 patients were randomized and observed over 42 days after a single im injection of 3, 6, 9, or 12 mg Sandostatin LAR. In the second study, 15 patients were randomized and observed over 60 days after a single im injection of either 20 or 30 mg Sandostatin LAR. Assessments of 12-h GH and octreotide profiles and adverse events were made on day -14 (during treatment with Sandostatin, sc); day 0 (off treatment after wash-out period); days 1, 7, 14, 21, 28, 35, and 42; and, for study 2, also on days 49 and 60 after the im injection. Only injections of 20 or 30 mg were followed by a suppression of basal GH and insulin-like growth factor I to levels comparable to those seen during sc treatment. The suppression of mean GH to less than 5 micrograms/L lasted for 4 weeks in the group receiving 20 mg and for at least 6 weeks in those given 30 mg Sandostatin LAR. The pharmacokinetic profile fitted a biphasic drug release model previously described for peptides in similar drug delivery systems. Serum concentrations correlated with the im administered dose. Suppression of GH and insulin-like growth factor I was achieved at serum octreotide concentrations exceeding approximately 600 ng/L. Tolerability was good. Sandostatin LAR holds promise as a valuable drug for the treatment of acromegaly. The results of ongoing long term studies will provide further necessary knowledge of the drug.
善龙（Sandostatin LAR）是一种长效奥曲肽制剂，它是通过将药物与可生物降解的聚（丙交酯-乙交酯）-葡萄糖进行微囊化而研制的。我们研究了对在使用皮下注射奥曲肽进行2至4周预处理期间生长激素（GH）得到良好抑制的活动性肢端肥大症患者单次肌肉注射善龙的疗效和耐受性。进行了两项双盲研究。最初，14名患者被随机分组，并在单次肌肉注射3、6、9或12毫克善龙后观察42天。在第二项研究中，15名患者被随机分组，并在单次肌肉注射20或30毫克善龙后观察60天。在第-14天（皮下注射善龙治疗期间）、第0天（洗脱期后停药）、第1、7、14、21、28、35和42天对12小时GH和奥曲肽水平以及不良事件进行评估；对于研究2，在肌肉注射后的第49和60天也进行评估。只有注射20或30毫克后，基础GH和胰岛素样生长因子I才被抑制到与皮下注射治疗期间相当的水平。接受20毫克善龙治疗的组中，平均GH抑制至低于5微克/升持续4周，而接受30毫克善龙治疗的组中至少持续6周。药代动力学特征符合先前在类似药物递送系统中描述的肽的双相药物释放模型。血清浓度与肌肉注射剂量相关。当血清奥曲肽浓度超过约600纳克/升时，可实现对GH和胰岛素样生长因子I的抑制。耐受性良好。善龙有望成为治疗肢端肥大症的一种有价值的药物。正在进行的长期研究结果将提供关于该药物的更多必要知识。
