Kisspeptin

01 / Dosing schedule

Cited dosing

Kisspeptin has genuinely well-documented human dosing from the Imperial College programme, expressed in nmol/kg (KP-54) or microg/kg (KP-10) rather than flat milligram doses. KP-54 was given as a single subcutaneous IVF trigger at 1.6-12.8 nmol/kg; KP-10 was given intravenously.

Kisspeptin human dosing — KP-54 subQ (IVF) and KP-10 IV

Phase	Dose & frequency
KP-54 IVF trigger doses administered	1.6, 3.2, 6.4 and 12.8 nmol/kg as a single subcutaneous bolus
KP-54 additional registry dose arms	9.6 nmol/kg single trigger; and 9.6 nmol/kg followed by a further 9.6 nmol/kg 10 hours later
KP-54 injection volume	minimum 330 microL to maximum 530 microL, reconstituted in 0.9% saline
KP-10 IV bolus dose-response	0.01, 0.03, 0.1, 0.3, 1.0 and 3.0 microg/kg, given in ascending order
KP-10 high-dose infusion	3 microg/kg IV bolus then continuous IV infusion at 4 microg/kg/h
KP-10 pulse-frequency study	continuous IV infusion at 1.5 microg/kg/h
KP-10 preparation	1 mg lyophilised KP-10 diluted in 5 mL sterile normal saline (0.2 mg/mL)

Source · Jayasena CN, Abbara A, Comninos AN, et al. Kisspeptin-54 triggers egg maturation in women undergoing in vitro fertilization. J Clin Invest. 2014;124(8):3667-3677. ↗

Source indication · Triggering oocyte maturation in IVF (KP-54, NCT01667406) and reproductive-hormone pharmacology in healthy men (KP-10)

Injection frequency: KP-54 in IVF: a single trigger injection (one registry arm added a second injection 10 hours later). KP-10: acute IV bolus or continuous infusion within a single study session. Twice-weekly KP-54 for 8 weeks has been used in hypothalamic amenorrhoea.
Injection sites: n.a. — KP-54 was given as a single subcutaneous bolus injection and KP-10 intravenously; neither the JCI paper nor the trial registry names an anatomical injection site.

02 / Reconstitution

Reconstitution reference

Published trial procedure: KP-54 was reconstituted in 0.9% saline to give injection volumes of 330-530 microL. For KP-10, 1 mg lyophilised peptide was diluted in 5 mL sterile normal saline, giving 0.2 mg/mL.

Vial1 mg lyophilised kisspeptin-10 (KP-10 study procedure)

BAC water5 mL sterile 0.9% normal saline

Concentration0.2 mg/mL

Example dose0.03 microg/kg IV bolus (lowest dose that significantly raised LH)

On a U‑100 syringeweight-based; doses in the trial ran 0.01-3.0 microg/kg

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03 / Overview

Protocol overview

Kisspeptin is the KISS1 gene product that gates GnRH release. Two fragments dominate the human literature: kisspeptin-54 (metastin), with a reported human half-life of approximately 28 minutes, and the shorter kisspeptin-10, which clears much faster.

The best-known clinical application is IVF. In the Imperial College trial, KP-54 was given as a single subcutaneous bolus to trigger oocyte maturation instead of hCG, at 1.6 nmol/kg (2 patients), 3.2 nmol/kg (3), 6.4 nmol/kg (24) and 12.8 nmol/kg (24), on a background of 150 IU daily recombinant FSH and 0.25 mg daily GnRH antagonist, with luteal support of progesterone 400 mg twice daily and estradiol valerate 2 mg three times daily.

The registry record for the same programme lists additional arms at 9.6 nmol/kg, including a two-injection schedule with a second 9.6 nmol/kg dose 10 hours after the trigger, and a comparator arm receiving saline 10 hours later.

Kisspeptin-10 pharmacology in men used IV dosing: an ascending bolus series from 0.01 to 3.0 microg/kg, in which 0.03 microg/kg (23 pmol/kg) was already enough to raise LH significantly, plus a 3 microg/kg bolus followed by 4 microg/kg/h infusion, and a 1.5 microg/kg/h infusion for pulse-frequency work. Kisspeptin remains investigational with no approved product.

04 / References