title: Octreotide s.c. depot provides sustained octreotide bioavailability and similar IGF-1 suppression to octreotide LAR in healthy volunteers.
abstract: OBJECTIVE
  The aim was to assess the pharmacokinetics, pharmacodynamics, safety and tolerability of octreotide subcutaneous (s.c.) depot, a novel octreotide formulation.
  
  
  METHODS
  This was a phase I, randomized, open label study. After a single dose of octreotide immediate release (IR) 200 µg, subjects were randomized to one of eight groups to receive three monthly injections of octreotide s.c. depot A 10, 20 or 30 mg, B 30 mg, C 10, 20 or 30 mg or long acting octreotide (octreotide LAR) 30 mg.
  
  
  RESULTS
  One hundred and twenty-two subjects were randomized. For all depot variants, onset of octreotide release was rapid and sustained for up to 4 weeks. The relative octreotide bioavailability of depot variants vs. octreotide IR ranged from 0.68 (90% confidence interval [CI] 0.61, 0.76) to 0.91 (90% CI 0.81, 1.02) and, vs. octreotide LAR, was approximately four- to five-fold greater: 3.97 (90% CI 3.35, 4.71) to 5.27 ng ml(-1) h (90% CI 4.43, 6.27). All depot variants showed relatively rapid initial reductions of insulin-like growth factor 1 (IGF-1) compared with octreotide LAR. A trend of octreotide dose dependence was also indicated from the plasma concentrations and suppression of IGF-1. Maximum inhibition of IGF-1 at steady-state was highest for depot B and C. All depot treatments were well tolerated. The most frequent adverse events were gastrointestinal related.
  
  
  CONCLUSIONS
  Octreotide s.c. depot provides greater octreotide bioavailability with a more rapid onset and stronger suppression of IGF-1 than octreotide LAR in healthy volunteers.
authors.affiliation: Camurus AB, Lund.|Physical Chemistry, Lund University, Lund, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Tiberg
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: John
authors.initials: J
authors.lastname: Roberts
authors.affiliation: Camurus AB, Lund.
authors.forename: Camilla
authors.initials: C
authors.lastname: Cervin
authors.affiliation: Camurus AB, Lund.
authors.forename: Markus
authors.initials: M
authors.lastname: Johnsson
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Severine
authors.initials: S
authors.lastname: Sarp
authors.affiliation: Novartis Healthcare Pvt Ltd, Hyderabad, India.
authors.forename: Anadya Prakash
authors.initials: AP
authors.lastname: Tripathi
authors.affiliation: Camurus AB, Lund.
authors.forename: Margareta
authors.initials: M
authors.lastname: Linden
mesh_terms: D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001682:Biological Availability; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D065546:Drug Liberation; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D018931:Antineoplastic Agents, Hormonal; D003692:Delayed-Action Preparations; D007334:Insulin-Like Growth Factor I; D015282:Octreotide
keywords: FluidCrystal®; depot; formulation; injection; octreotide; subcutaneous