Oral Octreotide Absorption in Human Subjects: Comparable Pharmacokinetics to Parenteral Octreotide and Effective Growth Hormone Suppression

Context: 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. Objectives: The aim of the study was to determine oral octreotide absorption and effects on pituitary GH secretion compared to sc octreotide injection. Design: Four single-dose studies were conducted in 75 healthy volunteers. Intervention: Oral doses of 3, 10, or 20 mg octreotide and a single sc injection of 100 mu g octreotide were administered. \ Main Outcome Measure: 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 x 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. (J Clin Endocrinol Metab 97: 2362-2369, 2012)