title: Assessment of the absorption, metabolism and excretion of [¹⁴C]pasireotide in healthy volunteers using accelerator mass spectrometry.
abstract: OBJECTIVE
  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 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.
  
  
  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.
authors.affiliation: Drug Metabolism and Pharmacokinetics, Novartis Pharmaceuticals Corporation, East Hanover, NJ 07936, USA. tsuhan.lin@novartis.com
authors.forename: T-H
authors.initials: TH
authors.lastname: Lin
authors.forename: K
authors.initials: K
authors.lastname: Hu
authors.forename: J
authors.initials: J
authors.lastname: Flarakos
authors.forename: M
authors.initials: M
authors.lastname: Sharr-McMahon
authors.forename: J B
authors.initials: JB
authors.lastname: Mangold
authors.forename: H
authors.initials: H
authors.lastname: He
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000032:analysis / Q000493:pharmacokinetics*; D001682:Biological Availability; D001711:Biotransformation; D002250:Carbon Radioisotopes; D005243:Feces / Q000737:chemistry; D006207:Half-Life; D006801:Humans; D007279:Injections, Subcutaneous; D007408:Intestinal Absorption; D008297:Male; D008657:Metabolic Clearance Rate; D010949:Plasma / Q000737:chemistry; D017481:Receptors, Somatostatin / Q000819:agonists*; D013004:Somatostatin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics; D014556:Urine / Q000737:chemistry; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D002250:Carbon Radioisotopes; D017481:Receptors, Somatostatin; D013004:Somatostatin; C517782:pasireotide