Bronstein M, Musolino N, Jallad R, Cendros J M, Ramis J, Obach R, Leselbaum A, Catus F
Neuroendocrine Unit, Division of Endocrinology and Metabolism, University of Sao Paulo Medical School, Brazil.
Clin Endocrinol (Oxf). 2005 Nov;63(5):514-9. doi: 10.1111/j.1365-2265.2005.02372.x.
To investigate the pharmacokinetic profile of a prolonged release, aqueous Autogel formulation of the somatostatin analogue lanreotide (Lan-ATG).
A phase II, randomized, double-blind study, during which patients received 60, 90 or 120 mg Lan-ATG for four fixed administrations at 28-day intervals.
A total of 18 patients with acromegaly were recruited; six patients were randomized to each treatment.
Lanreotide minimum concentration (C(min)), maximum serum concentration (C(max)) and area under the concentration-time curve during a dosing interval (AUC(tau)) were assessed after a single dose and at steady state (ss). Serum GH and IGF-1 levels were assessed before each administration and at the end of the study.
After a single administration, dose proportionality for C(min,1), C(max) and AUC(tau) was demonstrated statistically. After repeated administrations, Lan-ATG exhibited linear pharmacokinetics over the dose range and ss values of C(min), C(max) and AUC(tau) increased in a dose-dependent, linear manner. Mean C(max,ss) values were only two- to fourfold greater than C(min,ss) values, and there was good control over the entire release profile. Serum levels of GH and IGF-1 declined over the course of the study and acromegaly symptoms improved. The treatment was well tolerated.
Lan-ATG showed linear pharmacokinetic profiles over the three dose levels after both single and repeated dosing, no initial burst effect and good control over the entire release profile. Despite the absence of dose adaptation, four injections of Lan-ATG were effective in lowering serum levels of GH and IGF-1.
研究生长抑素类似物兰瑞肽（Lan-ATG）的长效水性自凝胶制剂的药代动力学特征。
一项II期随机双盲研究，在此期间患者接受60、90或120mg Lan-ATG，每28天固定给药一次，共给药四次。
共招募了18例肢端肥大症患者；每组随机分配6例患者接受各治疗。
在单剂量给药后及稳态时评估兰瑞肽的最低浓度（C(min)）、最高血清浓度（C(max)）以及给药间隔期间的浓度-时间曲线下面积（AUC(tau)）。在每次给药前及研究结束时评估血清生长激素（GH）和胰岛素样生长因子-1（IGF-1）水平。
单次给药后，C(min,1)、C(max)和AUC(tau)的剂量比例关系经统计学验证。多次给药后，Lan-ATG在剂量范围内呈现线性药代动力学特征，C(min)、C(max)和AUC(tau)的稳态值呈剂量依赖性线性增加。平均C(max,ss)值仅比C(min,ss)值高两至四倍，且对整个释放过程有良好控制。在研究过程中血清GH和IGF-1水平下降，肢端肥大症症状改善。该治疗耐受性良好。
Lan-ATG在单次和多次给药后的三个剂量水平上均呈现线性药代动力学特征，无初始突释效应，且对整个释放过程有良好控制。尽管未进行剂量调整，但四次注射Lan-ATG可有效降低血清GH和IGF-1水平。
