Pharmacokinetics and Short-Term Metabolic Effects of Mammalian Cell-Derived Biosynthetic Human Growth Hormone in Man

Abstract

The pharmacokinetics and acute effects of an authentic recombinant DNA-derived human growth hormone (rhGH) produced by genetically engineered mammalian cells were determined in 12 healthy volunteers following intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) administration of 4IU (1.3 mg) hGH/m² body surface area. Following i.v. administration, apparent elimination half-life of rhGH was 18 min. Following i.m. administration, a mean peak serum concentration of 36.9 ng/ml (range 13-61 ng/ml) occurred at 3 h, and following s.c. administration, more sustained but lower serum concentrations occurred, with mean peak concentrations of 16.4 and 16.3 ng/ml at 4 and 6 h (ranges 9.0-27.5 ng/ml and 6.5-35.5 ng/ml at 4 and 6 h, respectively). The mean area under the curves was lower after s.c. (134 ± 48 ng·h·mH) than after i.m. (194 ± 48 ng·h·ml^-1) injections (p < 0.03). Comparable results were obtained for the same dose of rhGH given subcutaneously in concentrations of either 4 IU/ml or 10 IU/ml. Both i.m. and s.c. administrations caused similar increases in free fatty acids at 4 h and insulin-like growth factor I at 24 h. Insulin, C-peptide and blood glucose were almost unchanged during the first 4 h after administration, whereas leukocytes increased significantly (p < 0.0001). Local and systemic tolerance were good, and no adverse reactions were observed. In a GH-deficient child, hGH serum levels between 10 and 20 ng/ml were demonstrated for a period of 8 h after s.c. administration of 0.07 IU rhGH/kg body weight.

In Vivo and In Vitro Effects of Human Growth Hormone on Rat Intestinal Ion Transport

“…It should be noted that such an effect was obtained in a range of hormone concentrations which are well below those previously administered to human volunteers (20). Third, the dependency on Cl" of the electrical response to r-hGH represents clear-cut evidence in favor of the antisecretory nature of the hormone effect.…”

“…The apparently transient nature of the pro absorptive effect in vivo is well explained by the half-life of r-hGH, which is reported to be 18 min after i.v . administration (20). It should be noted that the pharmacokinetic features of r-hGH change, depending on the administration route , and more sustained concentrations may be achieved by intramuscular or s.c .…”

“…It should be noted that the pharmacokinetic features of r-hGH change, depending on the administration route , and more sustained concentrations may be achieved by intramuscular or s.c . compared with the i.v, administration (20) . This could allow an absorptive effect of longer duration compared with that observed by i.v.…”

“…The lack of side effects, even by the i.v. administration (20), together with the availability of r-hGH, make it an attractive tool to be used in the treatment of protracted and/or severe diarrhea.…”

Growth Hormone Treatment Adherence in Prepubertal and Pubertal Children with Different Growth Disorders

“…With the availability of recombinant hGH (rhGH) from 1985 [3,4], it has become possible to treat greater numbers of patients for a wider range of growth disorders. rhGH is used to treat growth hormone deficiency (GHD) in children and adults, and to promote growth in children with Turner syndrome (TS), chronic renal failure (CRF) and idiopathic short stature, and children born small for gestational age (SGA) who fail to demonstrate catch-up growth [5].…”