Long-acting forms of growth hormone-releasing hormone and growth hormone: effects in normal volunteers and adults with growth hormone deficiency.
BACKGROUND
Growth hormone (GH) replacement therapy in adults and children has found broad acceptance by endocrinologists and patients, but the need for daily injections remains a significant barrier to more widespread use. LONG-ACTING FORMULATIONS: Several approaches have been taken to develop long-acting forms of GH and to extend the half-life of GH-releasing factor. Each of these preparations has been tested in experimental animal models and found to extend the half-life of GH and GH-releasing hormone (GHRH) and to increase mean daily GH levels. Frequent sampling following administration of long-acting GHRH showed that the greatest increases occurred in trough GH levels, which increased 7.8-fold. The extended GH half-life and increased trough levels resulted in increases in insulin-like growth factor I (IGF-I) levels, which increased 1.4- to 4.1-fold and extended the duration of the IGF-I increase from 7 to 14 days. These increases in GH and IGF-I levels allow these compounds to be administered much less frequently, and several studies have shown that IGF-I levels can be maintained in a therapeutically effective range with much less frequent GH administration.


RESULTS
Complications other than those generally associated with GH therapy include nodule formation and lipoatrophy at the injection sites. One long-term study of a long-acting formulation demonstrated that growth could be effectively stimulated in GH-deficient children, but that the peak growth velocity was only about 80% of that seen following daily subcutaneous GH injections. Subcutaneous nodule formation in some patients may have contributed to noncompliance and thus to the difference in growth velocity.


CONCLUSIONS
Different types of GH and GHRH formulations have been developed with extended half-lives. In general, these preparations are pharmacokinetically and pharmacodynamically effective, extend GH half-lives with longer sustained elevation of IGF-I and permit much less frequent GH administration. Thus, it may be possible to develop a therapeutically effective form of GH for use in long-term treatment. The precise efficacy and safety assessments to use in monitoring long-term GH administration have not been definitively established.
Clemmons
David R
DR
School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA. endo@med.unc.edu
D000328:Adult; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D013006:Growth Hormone / Q000008:administration & dosage* / Q000627:therapeutic use; D013007:Growth Hormone-Releasing Hormone / Q000008:administration & dosage*; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D008661:Metabolism, Inborn Errors / Q000188:drug therapy*
D003692:Delayed-Action Preparations; D019382:Human Growth Hormone; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone