Tiberg Fredrik, Roberts John, Cervin Camilla, Johnsson Markus, Sarp Severine, Tripathi Anadya Prakash, Linden Margareta
Camurus AB, Lund.
Physical Chemistry, Lund University, Lund, Sweden.
Br J Clin Pharmacol. 2015 Sep;80(3):460-72. doi: 10.1111/bcp.12698. Epub 2015 Aug 6.
The aim was to assess the pharmacokinetics, pharmacodynamics, safety and tolerability of octreotide subcutaneous (s.c.) depot, a novel octreotide formulation.
This was a phase I, randomized, open label study. After a single dose of octreotide immediate release (IR) 200 µg, subjects were randomized to one of eight groups to receive three monthly injections of octreotide s.c. depot A 10, 20 or 30 mg, B 30 mg, C 10, 20 or 30 mg or long acting octreotide (octreotide LAR) 30 mg.
One hundred and twenty-two subjects were randomized. For all depot variants, onset of octreotide release was rapid and sustained for up to 4 weeks. The relative octreotide bioavailability of depot variants vs. octreotide IR ranged from 0.68 (90% confidence interval [CI] 0.61, 0.76) to 0.91 (90% CI 0.81, 1.02) and, vs. octreotide LAR, was approximately four- to five-fold greater: 3.97 (90% CI 3.35, 4.71) to 5.27 ng ml(-1) h (90% CI 4.43, 6.27). All depot variants showed relatively rapid initial reductions of insulin-like growth factor 1 (IGF-1) compared with octreotide LAR. A trend of octreotide dose dependence was also indicated from the plasma concentrations and suppression of IGF-1. Maximum inhibition of IGF-1 at steady-state was highest for depot B and C. All depot treatments were well tolerated. The most frequent adverse events were gastrointestinal related.
Octreotide s.c. depot provides greater octreotide bioavailability with a more rapid onset and stronger suppression of IGF-1 than octreotide LAR in healthy volunteers.
旨在评估一种新型奥曲肽制剂——奥曲肽皮下长效注射剂的药代动力学、药效学、安全性及耐受性。
这是一项I期随机开放标签研究。在单次注射200μg即释型奥曲肽后，受试者被随机分为8组，分别接受每三个月一次的皮下注射奥曲肽长效注射剂A 10mg、20mg或30mg，B 30mg，C 10mg、20mg或30mg，或长效奥曲肽（奥曲肽LAR）30mg。
122名受试者被随机分组。对于所有长效注射剂变体，奥曲肽释放迅速且可持续长达4周。长效注射剂变体相对于即释型奥曲肽的奥曲肽相对生物利用度范围为0.68（90%置信区间[CI] 0.61, 0.76）至0.91（90% CI 0.81, 1.02），相对于奥曲肽LAR，约高四至五倍：3.97（90% CI 3.35, 4.71）至5.27 ng ml⁻¹ h（90% CI 4.43, 6.27）。与奥曲肽LAR相比，所有长效注射剂变体均显示胰岛素样生长因子1（IGF-1）相对迅速的初始降低。从血浆浓度和IGF-1抑制情况也表明了奥曲肽剂量依赖性趋势。在稳态时，长效注射剂B和C对IGF-1的最大抑制作用最高。所有长效注射剂治疗耐受性良好。最常见的不良事件与胃肠道有关。
在健康志愿者中，奥曲肽皮下长效注射剂比奥曲肽LAR具有更高的奥曲肽生物利用度，起效更快，对IGF-1的抑制作用更强。
