Assessment of the absorption, metabolism and excretion of [ 14C]pasireotide in healthy volunteers using accelerator mass spectrometry

摘要

Purpose: 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. Methods: 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. Results: [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 AUC0-24h 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. Conclusions: 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.