Pharmacokinetics and GH-stimulating activity of Hexarelin by different administration routes

Source: Ghigo E. et al., The Journal of Clinical Endocrinology & Metabolism, 1994, Vol. 78(3), pp. 693–698, 10.1210/jcem.78.3.8126137


Study Objective

To evaluate the GH-stimulating activity of Hexarelin - a new synthetic hexapeptide from the GHRP class - after different routes of administration: intravenous (IV), subcutaneous (SC), intranasal (IN), and oral (PO).

Hexarelin is a stable analog of GHRP-6, with higher resistance to degradation and a more pronounced potential to stimulate growth hormone (GH) secretion in humans. The objective is to investigate the dose-dependency, bioavailability, and reproducibility of the response, compared to GHRH.


Study Design

  • Type: clinical, interventional, crossover study

  • Participants: 12 healthy volunteers (6 men, 6 women; 20–35 years old)

  • Interventions:

    • IV: 1 and 2 µg/kg Hexarelin

    • SC: 1.5 and 3 µg/kg

    • IN: 20 µg/kg

    • PO: 20 and 40 mg

    • Controls: IV saline and GHRH (1 µg/kg)

  • Follow-up duration: 180 minutes

  • Measured parameters:

    • Serum GH levels (Cmax, AUC, Tmax)

    • Prolactin (PRL)

    • Biological availability (SC, IN, PO vs. IV)

    • Reproducibility of response (repeated IV dose)


Main Results

GH Release and Dose-Dependency

  • IV Hexarelin (1 µg/kg) induced a GH response ~2 times higher than that of GHRH (AUC 3175 ± 506 vs. 1544 ± 161 µg·min/L, p<0.001).

  • 2 µg/kg IV led to an additional increase (AUC 4422 ± 626 µg·min/L).

  • SC administration: dose-dependent GH response – AUC 3180 ± 392 (1.5 µg/kg) and 4459 ± 566 (3 µg/kg).

  • IN 20 µg/kg: AUC 2642 ± 452 µg·min/L – similar to 1 µg/kg IV.

  • PO 20 and 40 mg: AUC 2278 ± 442 and 4079 ± 514 µg·min/L.

Bioavailability

  • SC: 77.0 ± 10.5%

  • IN: 4.8 ± 0.9%

  • PO: 0.3 ± 0.1%

Reproducibility

  • 2 µg/kg IV showed high reproducibility of the GH response (AUC 4016 ± 563 vs. 3959 ± 803 µg·min/L for the repeated dose).

Prolactin

  • Hexarelin caused a slight, transient increase in PRL, within normal values.

Tolerability

  • No serious adverse reactions; mild, transient flushing or drowsiness were observed in some participants.


Conclusions

  • Hexarelin is a potent and dose-dependent GH secretagogue with high reproducibility of effect.

  • It shows a stronger GH response than GHRH and good activity with SC and IN administration.

  • Oral activity is limited but significant at high doses.

  • Suitable for studies on GH secretion and potential application in GH deficiency.


Limitations

  • Small sample size (n=12), short follow-up (180 min).

  • Lack of long-term data on efficacy and safety.


Practical Implications

  • Hexarelin is a potent and reliable GH secretagogue with a dose-dependent effect and high bioavailability upon SC administration.

  • It represents a valuable tool for studying the GH-IGF-1 axis and a possible candidate for therapeutic stimulation in GH deficiency.