title: Oral octreotide absorption in human subjects: comparable pharmacokinetics to parenteral octreotide and effective growth hormone suppression.
abstract: BACKGROUND
  Oral administration of a novel octreotide formulation enabled its absorption to the systemic circulation, exhibiting blood concentrations comparable to those observed with injected octreotide and maintaining its biological activity.
  
  
  OBJECTIVE
  The aim of the study was to determine oral octreotide absorption and effects on pituitary GH secretion compared to sc octreotide injection.
  
  
  METHODS
  Four single-dose studies were conducted in 75 healthy volunteers.
  
  
  METHODS
  Oral doses of 3, 10, or 20 mg octreotide and a single sc injection of 100 μg octreotide were administered.
  
  
  METHODS
  We measured the pharmacokinetic profile of orally administrated octreotide and the effect of octreotide on basal and stimulated GH secretion.
  
  
  RESULTS
  Both oral and sc treatments were well tolerated. Oral octreotide absorption to the circulation was apparent within 1 h after dose administration. Escalating oral octreotide doses resulted in dose-dependent increased plasma octreotide concentrations, with an observed rate of plasma decay similar to parenteral administration. Both 20 mg oral octreotide and injection of 0.1 mg sc octreotide resulted in equivalent pharmacokinetic parameters [mean peak plasma concentration, 3.77 ± 0.25 vs. 3.97 ± 0.19 ng/ml; mean area under the curve, 16.2 ± 1.25 vs. 12.1 ± 0.45 h × ng/ml); and median time ≥ 0.5 ng/ml, 7.67 vs. 5.88 h, respectively). A single dose of 20 mg oral octreotide resulted in basal (P < 0.05) and GHRH-stimulated (P < 0.001) mean GH levels suppressed by 49 and 80%, respectively.
  
  
  CONCLUSIONS
  The results support an oral octreotide alternative to parenteral octreotide treatment for patients with acromegaly.
authors.affiliation: Chiasma, 10 Hartom Street, Jerusalem 45182, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Tuvia
authors.forename: J
authors.initials: J
authors.lastname: Atsmon
authors.forename: S L
authors.initials: SL
authors.lastname: Teichman
authors.forename: S
authors.initials: S
authors.lastname: Katz
authors.forename: P
authors.initials: P
authors.lastname: Salama
authors.forename: D
authors.initials: D
authors.lastname: Pelled
authors.forename: I
authors.initials: I
authors.lastname: Landau
authors.forename: I
authors.initials: I
authors.lastname: Karmeli
authors.forename: M
authors.initials: M
authors.lastname: Bidlingmaier
authors.forename: C J
authors.initials: CJ
authors.lastname: Strasburger
authors.forename: D L
authors.initials: DL
authors.lastname: Kleinberg
authors.forename: S
authors.initials: S
authors.lastname: Melmed
authors.forename: R
authors.initials: R
authors.lastname: Mamluk
mesh_terms: D000042:Absorption; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D019382:Human Growth Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D007263:Infusions, Parenteral; D055104:Infusions, Subcutaneous; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D035842:Research Subjects; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018931:Antineoplastic Agents, Hormonal; D019382:Human Growth Hormone; D015282:Octreotide