Pharmacokinetics and GH-Stimulating Activity of Hexarelin via Different Routes of Administration

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 novel synthetic hexapeptide of the GHRP class – following 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 for stimulating growth hormone (GH) secretion in humans. The aim was to investigate the dose-dependence, bioavailability, and reproducibility of the response, compared with GHRH.

Study Design

• Type: clinical, interventional, crossover study

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

• 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 (C_max, AUC, T_max)

  • Prolactin (PRL)

  • Biological bioavailability (SC, IN, PO relative to IV)

  • Reproducibility of the response (repeat IV dose)

Key Results

GH Release and Dose-Dependence

• IV Hexarelin (1 µg/kg) induces 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 results in a further 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 shows high reproducibility of the GH response (AUC 4016 ± 563 vs. 3959 ± 803 µg·min/L on repeat dosing).

Prolactin

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

Tolerability

• No serious adverse reactions were observed; mild, short-lived flushing or drowsiness was noted 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 via SC and IN administration.

• Oral activity is limited but significant at high doses.

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

Limitations

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

• Lack of long-term efficacy and safety data.

Practical Significance

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

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