A model-based analysis to guide gonadotropin-releasing hormone receptor antagonist use for management of endometriosis.

ABSTRACT:

Aims

To identify linzagolix doses, an oral GnRH receptor antagonist, that effectively lower oestradiol (E2) to relieve endometriosis-related pelvic pain without compromising bone health.

Methods

Integrated statistical, pharmacokinetic-pharmacodynamic and systems pharmacology models were developed from Phase 1 and 2 clinical trial data in healthy volunteers and patients, receiving linzagolix 25-200 mg daily or placebo, and analysed simultaneously. The main outcome measures were pelvic pain scores for dysmenorrhoea, nonmenstrual pelvic pain (NMPP), uterine bleeding and lumbar spine bone mineral density (BMD).

Results

Linzagolix pharmacokinetics were described by a 2-compartment model with sequential zero/first-order absorption process (CL/F: 0.422 L/h). E2 changes over

SUBMITTER: Pohl O 

PROVIDER: S-EPMC9306723 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature