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

Article date: September 2015

By: Fredrik Tiberg, John Roberts, Camilla Cervin, Markus Johnsson, Severine Sarp, Anadya Prakash Tripathi, Margareta Linden, in Volume 80, Issue 3, pages 460-472

Aims

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.

DOI: 10.1111/bcp.12698

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