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Updated: Aug 24, 2026

A Standardized Ex Vivo Porcine Oromucosal Model for Evaluating Peptide Fluxes
Published on: June 9, 2026
Population pharmacokinetic modeling of a subcutaneous depot for GnRH antagonist degarelix
Christoffer W Tornøe1, Henrik Agersø, Henrik A Nielsen
1Clinical Pharmacology and Experimental Medicine, Ferring Pharmaceuticals A/S, Copenhagen, Denmark. christoffer.tornoe@ferring.com
Purpose:
The objective of this study is to develop a population pharmacokinetic (PK) model that describes the subcutaneous (SC) depot formation of gonadotropin-releasing hormone (GnRH) antagonist degarelix, which is being developed for treatment of prostate cancer, exhibiting dose-volume and dose-concentration dependent absorption.
Methods:
The PK analysis is made in NONMEM through joint analysis of data from two phase I clinical studies; an intravenous infusion study and a single SC dose escalation study. The SC absorption is modeled using an approximation to Ficks' second law of diffusion out of a spherical depot. The dose-volume effect on the SC release is estimated using a B-spline basis whereas the bioavailability is modeled as a function of the dose-concentration.
Results:
The SC depot model is approximated by using two concentric spherical compartments for the SC absorption combined with a two-compartment disposition model. The results indicate that the volume effect is most apparent at low injection volumes whereas the effect is diminishing at higher injection volumes. The dose-concentration effect on the bioavailability is estimated to decrease at increasing dose-concentrations.
Conclusions:
The presented SC depot model describes the PK profile of GnRH antagonist degarelix. This modeling approach might also be applicable for other depot-formulated drugs exhibiting complex PK profiles.
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