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. Safety: 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.

1.
Reiter EO, Attie KM, Moshang T Jr, Silverman BL, Kemp SF, Neuwirth RB, Ford KM, Saenger P, and the Genentech Inc.-Alkermes Inc. Collaborative Study Group: A multicenter study of the efficacy and safety of sustained release GH in the treatment of naive pediatric patients with GH deficiency. J Clin Endocrinol Metab 2001;86:4700–4706.
2.
Cook DM, Biller BM K, Vance ML, Hoffman AR, Phillips LS, Ford PKM, Benziger DP, Illeperuma SL, Blethen KM, Attie KM, Dao LN, Reimann JD, Fielder PJ: The pharmacokinetic and pharmacodynamic characteristics of a long-acting growth hormone (GH) preparation (Nutropin Depot) in GH-deficient adults. Clin Endocrinol Metab 2002;87:4508–4514.
3.
Hoffman AR, Biller BMK, Cook D, Baptista J, Silverman BL, Le Dao Attie KM, Fielder P, Maneatis T, Lippe B, for the Genentech Adult Growth Hormone Deficiency Study Group: Efficacy of a long-acting growth hormone (GH) preparation in patients with adult GH deficiency. J Clin Endocrinol Metab 2005;90:6431–6440.
4.
Munafo A, Nguyen TX, Papasouliotis O, Lecuelle H, Priestly A, Thorner MO: Polyethylene glycol-conjugated growth hormone-releasing hormone is long acting and stimulates GH in healthy young and elderly subjects. Eur J Endocrinol 2005;153:249–256.
5.
Ionescu M, Frohman L: Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. J Clin Endocrinol Metab 2006;91:4792–4797.
6.
Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA: Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. Clin Endocrinol Metab 2006;91:799–805.
7.
Bidlingmaier M, Kim J, Savoy C, Kim MJ, Ebrecht N, de la Motte S, Strasburger, CJ: Comparative pharmacokinetics and pharmacodynamics of a new sustained-release growth hormone (GH), LB03002, versus daily GH in adults with GH deficiency. J Clin Endocrinol Metab 2006;91:2926–2930.
8.
Harris PE, Didier E, Boonen A, Kantaridis C, Weissgerber G, Abs R: The pharmacokinetics, pharmacodynamics and safety of pegylated recombinant human growth hormone after single subcutaneous injections in adult male patients with growth hormone deficiency. 88th Annual Meeting of the Endocrine Society Program and Abstracts. 2006 Boston, MA.
9.
Harris PE, Didier E, Kantaridis C, Boonen A, Weissgerber G:First in-human study of pegylated recombinant human growth hormone. 88th Annual Meeting of the Endocrine Society Program and Abstracts. 2006 Boston, MA.
10.
Xie R, Didier E, Harris PE, Milligan PA, Karlsson MO: Population pharmacokinetic/pharmacodynamic analysis for pegylated recombinant human growth hormone (PHA-794428) in healthy male volunteers. 88th Annual Meeting of the Endocrine Society Program and Abstracts. 2006 Boston, MA.
11.
Harris PE, Didier E, Kantaridis C, Boonen A, Weissgerber G: First in human study of pegylated recombinant human growth hormone. Horm Res 2006;65(suppl 4):30.
12.
Harris PE, Didier E, Boonen A, Kantaridis C, Weissgerber G, Abs R: The pharmacokinetics, pharmacodynamics and safety of pegylated recombinant human growth hormone after single subcutaneous injections in adult male patients with growth hormone deficiency. Horm Res 2006;65(suppl 4):148.
13.
Govardhan C, Khalaf N, Jung CW, Simeone B, Higbie A, Qu S, Chemmalil L, Pechenov S, Basu SK, Margolin AL: Novel long acting crystal formation of human growth hormone. Pharm Res 2005;22:1461–1470.
14.
Cox GN, Rosendahl MS, Chilpala EA, Smith DJ, Carlson SJ, Doherty DH: A long acting, mono-PEGylated human growth hormone analog is a potent stimulator of weight gain and bone growth in hypophysectomized rats. Endocrinology 2007;248:1590–1597.
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