Antonijoan R M, Barbanoj M J, Cordero J A, Peraire C, Obach R, Vallès J, Chérif-Cheikh R, Torres M-L, Bismuth F, Montes M
Centre d'Investigació de Medicaments, Institute of Research, Servei de Farmacologia Clínica, Hospital of Santa Creu and Sant Pau, Departament de Farmacologia i Terapèutica, UAB Barcelona, Spain.
J Pharm Pharmacol. 2004 Apr;56(4):471-6. doi: 10.1211/0022357023123.
The pharmacokinetics/tolerability of lanreotide Autogel have been evaluated. Healthy volunteers (n = 24) first received immediate-release lanreotide as a single subcutaneous (s.c.) injection. After two days, 40 or 60 mg lanreotide Autogel was injected subcutaneously. Blood was sampled at various intervals for 56 days. Systemic/local adverse events and changes in biological profile/vital signs were recorded. Lanreotide Autogel produced a prolonged-release pharmacokinetic profile: mean area under the serum concentration-time curve from time 0 to infinity (AUC) was 53.73 +/- 8.99 and 79.48 +/- 13.06 ng mL(-1) day for 40 and 60 mg, respectively, mean peak serum concentration (C(max)) was 4.38 +/- 2.91 and 5.71 +/- 3.52 ng mL(-1), respectively, median time to reach C (minimum-maximum) was 0.50 (0.083-18.0) and 0.38 (0.083-9.01) days, respectively, mean apparent elimination half-life was 21.63 +/- 9.42 and 22.01 +/- 9.87 days, respectively, and relative bioavailability was 0.93 +/- 0.12 and 0.82 +/- 0.15, respectively. Thus, lanreotide Autogel exhibited linear pharmacokinetics for the doses studied. Pharmacokinetic profiles were similar in both genders, apart from statistically significant differences in C(max) and C(max)/AUC. The Autogel formulation of lanreotide was well tolerated, with systemic adverse events being mild/moderate. Erythema and a painless subcutaneous induration were the most common local adverse events. Lanreotide Autogel provided a prolonged dosing interval and good tolerability for treating acromegaly and carcinoid syndrome.
已对兰瑞肽长效凝胶剂的药代动力学/耐受性进行了评估。健康志愿者（n = 24）首先接受速释兰瑞肽单次皮下注射。两天后，皮下注射40或60mg兰瑞肽长效凝胶剂。在56天内的不同时间间隔采集血样。记录全身/局部不良事件以及生物学指标/生命体征的变化。兰瑞肽长效凝胶剂呈现出缓释药代动力学特征：从时间0至无穷大的血清浓度-时间曲线下平均面积（AUC），40mg剂量组为53.73±8.99 ng·mL⁻¹·天，60mg剂量组为79.48±13.06 ng·mL⁻¹·天；平均血清峰值浓度（C(max)），40mg剂量组为4.38±2.91 ng·mL⁻¹，60mg剂量组为5.71±3.52 ng·mL⁻¹；达到C（最小-最大）的中位时间，40mg剂量组为0.50（0.083 - 18.0）天，60mg剂量组为0.38（0.083 - 9.01）天；平均表观消除半衰期，40mg剂量组为21.63±9.42天，60mg剂量组为22.01±9.87天；相对生物利用度，40mg剂量组为0.93±0.12，60mg剂量组为0.82±0.15。因此，兰瑞肽长效凝胶剂在所研究的剂量下呈现线性药代动力学。除C(max)和C(max)/AUC存在统计学显著差异外，两性的药代动力学特征相似。兰瑞肽长效凝胶剂耐受性良好，全身不良事件为轻度/中度。红斑和无痛性皮下硬结是最常见的局部不良事件。兰瑞肽长效凝胶剂为肢端肥大症和类癌综合征的治疗提供了延长的给药间隔和良好的耐受性。
