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

• Published in: Cancer chemotherapy and pharmacology Vol. 72; no. 1; pp. 181 - 188
• Main Authors: Lin, T.-H., Hu, K., Flarakos, J., Sharr-McMahon, M., Mangold, J. B., He, H., Wang, Y.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.07.2013; Springer; Springer Nature B.V
• Subjects: Adolescent; Adult; Antineoplastic agents; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - analysis; Antineoplastic Agents - pharmacokinetics; Biological and medical sciences; Biological Availability; Biotransformation; Cancer Research; Carbon Radioisotopes; Feces - chemistry; Half-Life; Humans; Injections, Subcutaneous; Intestinal Absorption; Male; Medical sciences; Medicine; Medicine & Public Health; Metabolic Clearance Rate; Oncology; Original Article; Pharmacology. Drug treatments; Pharmacology/Toxicology; Plasma - chemistry; Receptors, Somatostatin - agonists; Somatostatin - administration & dosage; Somatostatin - adverse effects; Somatostatin - analogs & derivatives; Somatostatin - analysis; Somatostatin - pharmacokinetics; Urine - chemistry; Young Adult; Accelerator mass spectrometry (AMS); Healthy volunteers; Absorption, distribution, metabolism and excretion (ADME); Pasireotide; Pharmacokinetics; Human; Evaluation; Excretion; Absorption distribution metabolism and excretion (ADME); Healthy subject; Peptide hormone; Exploration; Metabolism; Neuropeptide; Absorption; Analog; Distribution; Somatostatin; Mass spectrometry; Accelerator
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-013-2183-0

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 [ 14 C]pasireotide. Methods Blood, plasma, urine and feces were collected for 240 h post-dose and analyzed for total 14 C and metabolite profile by accelerator mass spectrometry (AMS) or high-performance liquid chromatography–AMS. Parent drug levels were analyzed by radioimmunoassay. Results [ 14 C]pasireotide was rapidly absorbed, with a mean peak plasma 14 C concentration of 16.6 ± 5.28 ngEq/mL at 0.5 h in plasma. The parent drug to total 14 C 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 [ 14 C]pasireotide was detected. Unchanged [ 14 C]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 [ 14 C]pasireotide 600 μg sc administered to healthy male subjects was rapidly absorbed and excreted in its unchanged form primarily via the hepatic route.