Clemmons David R
School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
Horm Res. 2007;68 Suppl 5:178-81. doi: 10.1159/000110620. Epub 2007 Dec 10.
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.
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.
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.
生长激素（GH）替代疗法在成人和儿童中已被内分泌学家和患者广泛接受，但每日注射的需求仍然是其更广泛应用的重大障碍。
已经采取了几种方法来开发长效形式的GH并延长生长激素释放因子的半衰期。这些制剂中的每一种都已在实验动物模型中进行了测试，发现可延长GH和生长激素释放激素（GHRH）的半衰期，并提高每日平均GH水平。长效GHRH给药后的频繁采样表明，最大的增加发生在谷值GH水平，其增加了7.8倍。GH半衰期的延长和谷值水平的增加导致胰岛素样生长因子I（IGF-I）水平升高，升高了1.4至4.1倍，并将IGF-I升高的持续时间从7天延长至14天。GH和IGF-I水平的这些增加使得这些化合物的给药频率可以大大降低，并且几项研究表明，通过较少频率的GH给药可以将IGF-I水平维持在治疗有效范围内。
除了那些通常与GH治疗相关联的并发症外，还包括注射部位的结节形成和脂肪萎缩。一项关于长效制剂的长期研究表明，生长激素缺乏的儿童的生长可以得到有效刺激，但峰值生长速度仅约为每日皮下注射GH后所见速度的80%。一些患者的皮下结节形成可能导致了不依从性，从而导致了生长速度的差异。
已经开发出具有延长半衰期的不同类型的GH和GHRH制剂。一般来说，这些制剂在药代动力学和药效学上是有效的，延长了GH半衰期，使IGF-I持续升高更长时间，并允许更少频率的GH给药。因此，有可能开发出一种用于长期治疗的治疗有效的GH形式。用于监测长期GH给药的精确疗效和安全性评估尚未最终确定。
