Pharmacokinetics, Pharmacodynamics, and Efficacy of a Novel Long-Acting Human Growth Hormone: Fc Fusion Protein

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• 作者：Su Jin Kim ; Hyun-Hee Kwak ; Sung Yoon Cho ; Young Bae Sohn ; Sung Won Park ; Rimm Huh ; Jinsup Kim ; Ah-ra Ko ; Dong-Kyu Jin
• 刊名：Molecular Pharmaceutics
• 出版年：2015
• 出版时间：October 5, 2015
• 年：2015
• 卷：12
• 期：10
• 页码：3759-3765
• 全文大小：390K
• ISSN：1543-8392

文摘

The current recombinant human growth hormone (rhGH) therapy requires daily subcutaneous (sc) injections, which results in poor patient compliance, especially in young children. To reduce the dosing frequency, we generated a chimeric protein of rhGH and the Fc-domain of immunoglobulin G (IgG) (rhGH-Fc). The pharmacokinetics and pharmacodynamics of sc-injected rhGH-Fc were assessed in male Sprague鈥揇awley rats and hypophysectomized rats, respectively. A single sc injection of rhGH-Fc at a dose of 0.2 mg/kg slowly reached a C_max of 16.80 ng/mL and remained for 7 days with a half-life of 51.1 h. Conversely, a single sc injection of rhGH 0.2 mg/kg rapidly reached a C_max of 46.88 ng/mL and declined with a half-life of 0.55 h to baseline values in 4 h. In the efficacy study, the sc-injected rhGH-Fc induced rapid weight gain and tibial width growth at a dose of 240 渭g/animal. The effect of two injections of rhGH-Fc separated by 1 week was comparable to that of the same dose of 14 daily injections of rhGH. The rhGH-Fc is a novel candidate for long-acting rhGH therapy with more convenient weekly administration, as it reduces glomerular filtration and receptor-mediated clearance while allowing for the rapid reversal of potential adverse events.