Drug Metabolism and Pharmacokinetics, Novartis Pharmaceuticals Corporation, East Hanover, NJ 07936, USA.
Cancer Chemother Pharmacol. 2013 Jul;72(1):181-8. doi: 10.1007/s00280-013-2183-0. Epub 2013 May 17.
Pasireotide (SOM230) is a multireceptor-targeted somatostatin analog designed to have a broader somatostatin receptor binding profile than other currently available somatostatin analogs. The purpose of this study was to evaluate the absorption, metabolism and excretion of pasireotide in healthy male subjects (N = 4) following a single, subcutaneous (sc), 600 μg dose of [¹⁴C]pasireotide.
Blood, plasma, urine and feces were collected for 240 h post-dose and analyzed for total ¹⁴C and metabolite profile by accelerator mass spectrometry (AMS) or high-performance liquid chromatography-AMS. Parent drug levels were analyzed by radioimmunoassay.
[¹⁴C]pasireotide was rapidly absorbed, with a mean peak plasma ¹⁴C concentration of 16.6 ± 5.28 ngEq/mL at 0.5 h in plasma. The parent drug to total ¹⁴C AUC(0-24h) ratio was 1.08, indicating that little metabolite was present in plasma up to 24 h post-dose. In pooled plasma samples (0-12 h), only unchanged [¹⁴C]pasireotide was detected. Unchanged [¹⁴C]pasireotide accounted for approximately 84 % of total excretion (feces and urine). Approximately 56 % of the administered radioactive dose was recovered within 240 h, eliminated primarily in feces (48.3 ± 8.16 %) and minimally in urine (7.63 ± 2.03 %). No serious adverse events were reported.
A single dose of [¹⁴C]pasireotide 600 μg sc administered to healthy male subjects was rapidly absorbed and excreted in its unchanged form primarily via the hepatic route.
帕瑞肽（SOM230）是一种多受体靶向生长抑素类似物，与其他现有的生长抑素类似物相比，其生长抑素受体结合谱更广。本研究旨在评估健康男性受试者（N=4）单次皮下（sc）给予 600μg[¹⁴C]帕瑞肽后的吸收、代谢和排泄情况。
在给药后 240 h 内收集血液、血浆、尿液和粪便，并通过加速质谱仪（AMS）或高效液相色谱-AMS 分析总¹⁴C 和代谢产物谱。通过放射免疫分析法分析母体药物水平。
[¹⁴C]帕瑞肽吸收迅速，给药后 0.5 h 血浆中¹⁴C 峰浓度为 16.6±5.28ngEq/mL。母体药物与总¹⁴C AUC（0-24h）比值为 1.08，表明在给药后 24 h 内，血浆中几乎没有代谢产物。在合并的血浆样本（0-12 h）中，仅检测到未改变的[¹⁴C]帕瑞肽。未改变的[¹⁴C]帕瑞肽约占总排泄量（粪便和尿液）的 84%。给药后 240 h 内约有 56%的放射性剂量被回收，主要通过粪便（48.3±8.16%）排泄，尿液中排泄极微（7.63±2.03%）。未报告严重不良事件。
健康男性受试者单次皮下给予 600μg[¹⁴C]帕瑞肽后，以原形迅速吸收并主要通过肝途径排泄。
