The growth hormone-releasing activity of a synthetic hexapeptide in normal men and short statured children after oral administration.

It has been shown that iv GH-releasing peptide (GHRP; His-DTrp-Ala-Trp-DPhe-Lys-NH2) specifically releases GH in man. Because of the clinical value of having an orally active peptide to release GH, five normal men were given GHRP orally at dosages of 100 and 300 micrograms/kg. At the 300 micrograms/kg dosage, the GH rise was detectable at 30 min, peaked between 60-75 min, and gradually declined to the baseline level between 150-180 min. Peak GH levels rose 63- and 202-fold above the baseline after administration of 100 and 300 micrograms/kg GHRP, respectively. Nine short stature children with varying degrees of GH deficiency were also included in this study. All children had short stature, slow growth, and delayed bone age and were being treated with biosynthetic human GH. The studies were performed after stopping GH treatment for 2-3 weeks. The oral GHRP dose administered to all of the children was 300 micrograms/kg, because this dosage was found to consistently increase GH levels in adults. The magnitude and pattern of the GH response to oral GHRP in four of the nine children were essentially the same as those in the five normal men. In the other five children, the GH responses were low but still measurable in three and undetectable in two of the children. Serum immunoreactive GHRP (irGHRP) levels were measured before and at 15- to 30-min intervals 3-5 h after oral as well as iv bolus GHRP administration. For comparison of serum irGHRP and GH levels, results were included after iv bolus administration of 0.1, 0.3, and 1.0 micrograms/kg GHRP to normal men. Since 300 micrograms/kg oral GHRP released about the same amount of GH as 1 microgram/kg, iv, in normal men, it was calculated that oral GHRP has about 0.3% the activity of iv GHRP. After iv GHRP, the peak serum irGHRP levels were immediate and proportional to the dosage, and the disappearance rate decreased exponentially. Between 100-240 min, the mean serum irGHRP level was essentially the same and remained slightly elevated. After administration of 300 micrograms/kg GHRP orally to normal men, serum irGHRP was measurable within 15 min, the peak serum irGHRP level coincided with the GH rise at 60 min, and serum irGHRP levels fell more slowly than serum GH levels. The serum half-life was 20 min, and the distribution volume was 2.5 L after both oral and iv administration.(ABSTRACT TRUNCATED AT 400 WORDS)