Pharmacokinetic and Pharmacodynamic Characteristics of a Long-Acting Growth Hormone (GH) Preparation (Nutropin Depot) in GH-Deficient Children

• Published in: The journal of clinical endocrinology and metabolism Vol. 89; no. 7; pp. 3234 - 3240
• Main Authors: Kemp, S. F., Fielder, P. J., Attie, K. M., Blethen, S. L., Reiter, E. O., Ford, K. M., Marian, M., Dao, L. N., Lee, H. J., Saenger, P.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.07.2004; Copyright by The Endocrine Society
• Subjects: Biological and medical sciences; Child; Child, Preschool; Delayed-Action Preparations; Drug Administration Schedule; Endocrinopathies; Female; Fundamental and applied biological sciences. Psychology; Human Growth Hormone - administration & dosage; Human Growth Hormone - deficiency; Human Growth Hormone - pharmacokinetics; Humans; Insulin-Like Growth Factor Binding Protein 3 - blood; Insulin-Like Growth Factor I - metabolism; Male; Medical sciences; Metabolism, Inborn Errors - blood; Metabolism, Inborn Errors - drug therapy; Vertebrates: endocrinology; Human; Adenohypophyseal hormone; Preparation; Somatotropin hormone; Pharmacokinetics; Child; Endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2003-030825

Long-term GH replacement therapy is indicated for children with growth failure due to GH deficiency (GHD). We evaluated the feasibility of administering a long-acting GH preparation [Nutropin Depot (somatropin, rDNA origin) for injectable suspension] to prepubertal children with GHD by examining pharmacokinetic and pharmacodynamic response parameters after single or multiple doses. Data were collected from three studies involving 138 children treated with Nutropin Depot 0.75 mg/kg once per month, 0.75 mg/kg twice per month, or 1.5 mg/kg once per month. Twenty-two patients underwent intensive sampling to estimate mean peak serum GH concentrations (Cmax) and time to achieve Cmax for GH and IGF-I. Thereafter, weekly serum concentrations were measured and compared with baseline. Cmax and area under the curve were approximately proportional to the dose administered. Fractional area under the curve data indicate that at least 50% of GH exposure occurs during the first 2 d after administration. Serum GH levels remained above 1 μg/liter for 11–14 d. IGF-I levels remained above baseline for 16–20 d, but increases were not proportional to dose. After multiple doses over a 6-month period, peak and trough concentrations showed no progressive accumulation of GH, IGF-I, or IGF binding protein-3. Nutropin Depot administration once or twice per month provides serum levels of GH and IGF-I expected to promote growth, without accumulation of GH, IGF-I, or IGF binding protein-3, in children with GHD.