Octreotide s.c. depot provides sustained octreotide bioavailability and similar IGF‐1 suppression to octreotide LAR in healthy volunteers

Abstract

AimsThe aim was to assess the pharmacokinetics, pharmacodynamics, safety and tolerability of octreotide subcutaneous (s.c.) depot, a novel octreotide formulation.MethodsThis 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.ResultsOne 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.ConclusionsOctreotide s.c. depot provides greater octreotide bioavailability with a more rapid onset and stronger suppression of IGF-1 than octreotide LAR in healthy volunteers.

Nature‐Inspired Design and Application of Lipidic Lyotropic Liquid Crystals

“…The slow diffusive release of drugs has been harnessed in the formulation of long acting injectable depot systems for peptide hormones and pain medications to reduce the frequency of injection of these medicines to benefit the patient. In this way they present a viable alternative option to biodegradable polymers often used for such applications, which have disadvantages of the requirement for solvents in development, acidic breakdown products which can degrade the drug, and substantial regulatory hurdles.…”

Carcinoid Syndrome: A Review

“…Octreotide and Lanreotide have also been proven to inhibit tumor growth in randomized phase III trials [41]. A depot form of octreotide, which is administered intramuscularly on a monthly basis, as well as a long-acting formulation of lanreotide, is available for monthly injections [42]. Somatostatin analogs also inhibit gallbladder contractility, which can lead to gallstones or sludge.…”

Clinical Effects of Pantoprazole and Octreotide in Upper Gastrointestinal Hemorrhage

“…The halflife period of octreotide is more than 30 times that of natural demodicidin. 10 Octreotide can induces direct selective effects on vascular smooth muscles; significantly reduce the visceral blood flow; effectively inhibit the secretions of gastric acid, gastrin and protease; stimulate mucous secretion; protect the mucosal barrier; and recover mucous epithelial cells. 1112 More over, octreotide can increase the lower sphincter tension of the large esophagus, improve the gastric juice reflux, protect the esophagus mucosa and promote blood clot retraction and platelet aggregation.…”