Gonadorelin — pharmacology
Molecular targets, mechanism of action, pharmacokinetics and interactions as characterised in humans.
§2Pharmacology
§2.1Molecular targets
Table 2. Molecular targets recorded for Gonadorelin, with the character of the interaction and the potency where the Institute holds it.
| Target | Interaction | Note |
|---|---|---|
| Gonadotropin-releasing hormone receptor (GnRHR) | Agonist | Pituitary gonadotrope receptor; pulsatile stimulation maintains gonadotropin secretion while continuous stimulation downregulates it |
§2.2Mechanism of action
Gonadorelin stimulates pituitary release of luteinising hormone and follicle-stimulating hormone. Its pharmacology is dominated by a pattern dependence that is unusual and clinically decisive: pulsatile administration stimulates the axis, whereas continuous administration desensitises and downregulates it, producing the opposite effect. This is the basis both of pulsatile pump therapy for hypogonadotropic hypogonadism and of the long-acting GnRH agonists used for androgen deprivation. The Institute notes that supply-side material describing gonadorelin for "restarting" the axis rarely addresses the pattern dependence on which the outcome entirely depends.[1,2]
§2.3Pharmacokinetics
- Terminal half-life
- ≈2–4 min
- Time to maximum concentration
- immediate on intravenous administration
- Volume of distribution
- ≈9–15 L
- Plasma protein binding
- not extensively bound
- Clearance
- high
- Bioavailability
- well absorbed subcutaneously but the effect is confined to a single pulse
Rapid enzymatic cleavage, principally at the Trp3-Ser4 and Tyr5-Gly6 bonds, with renal excretion of fragments.
§2.4Interactions
- Glucocorticoids, dopamine agonists, spironolactone and digoxin all affect gonadotropin secretion and confound diagnostic interpretation
References cited on this page
References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.
- D’Hondt M, Bracke N, Taevernier L, Gevaert B, Verbeke F, Wynendaele E, De Spiegeleer B. Related impurities in peptide medicines. Journal of Pharmaceutical and Biomedical Analysis 2014;101:2–30. doi:10.1016/j.jpba.2014.06.012 · PMID 25044089
- Manning MC, Chou DK, Murphy BM, Payne RW, Katayama DS. Stability of protein pharmaceuticals: an update. Pharmaceutical Research 2010;27(4):544–575. doi:10.1007/s11095-009-0045-6 · PMID 20143256
Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.