title: Bioavailability of recombinant human growth hormone in different concentrations and formulations.
abstract: Whether the bioavailability of growth hormone depends on the concentration or formulation of the preparation was evaluated in 18 growth hormone-deficient patients. The design was a single-blinded, randomized cross-over study, where the patients were given a single, fixed dose subcutaneous injection of growth homrone (3 IU/m2) of 3 different preparations: (1) 4 IU/ml in a bicarbonate buffer dissolved in 0.9% benzyl alcohol (approximately 1.37 mg/ml), (2) 5.9 IU/ml in a phosphate buffer dissolved in 1.5% benzyl alcohol (approximately 2 mg/ml) and (3) 11 7 IU/ml in a phosphate buffer dissolved in 1.5% benzyl alcohol (approximately 4 mg/ml). Conventional growth hormone-therapy was withdrawn 2 days before each study period. Blood samples were drawn over a 24-hr period and assessed for growth hormone, serum insulin-like growth factor I (IGF-I), insulin and glucose. The geometric mean values (+/- geometric S.D) of the relative absorption fractions were F5.9 IU/4 IU = AUC5.9 IU/AUC4 IU = (+/- 1.139) (P = 0.66), F11.7 IU/AUC4 IU = AUC11.7 IU/AUC4 IU (1.14 +/- 1.21) (P = 0.009) AND F11.7 IU/5.9 IU = AUC11.7 IU/AUC5.9 IU = 1.12 (+/- 1.17) (P = 0.005), respectively. The 90% confidence intervals were contained within the limits of 0.80-1.25 accepted for bioequivalence. Geometric mean values (+/- geometric S.D.) of the relative observed maximum concentration, Cmax was for Cmax 5.9 IU/Cmax 4 IU = 1.04 (+/- 1.19) (P = 0.32), Cmax 11.7 IU/Cmax 4 IU = 1.24 (+/- 1.21) (P = 0.0002) and Cmax 11.7 IU/Cmax 5.9 IU = 1.19 (+/- 1.29) (P = 0.012). The median and the range values for the observed time to reach Cmax was tmax 5.9 IU/tmax 4 IU = 0.63 (0.04-1.00), tmax 11.7 IU/tmax 4 IU = 0.59 (0.06-1.0) and tmax 11.7 IU/tmax 5.9 IU = 0.90 (0.51-18.00). There were no significant differences in IGF-I, glucose and insulin profiles. Based on the upper limits of the 90% confidence intervals for relative AUC's the conclusion is that the three different preparations were bioequivalent.
authors.affiliation: Medical Department M (Endocrinology and Diabetes), Aarhus Kommunehospital, Aarhus University, Denmark.
authors.forename: N
authors.initials: N
authors.lastname: Vahl
authors.forename: S B
authors.initials: SB
authors.lastname: Jensen
authors.forename: M H
authors.initials: MH
authors.lastname: Rasmussen
authors.forename: S
authors.initials: S
authors.lastname: Susgaard
authors.forename: J O
authors.initials: JO
authors.lastname: Jørgensen
authors.forename: J S
authors.initials: JS
authors.lastname: Christiansen
authors.forename: U F
authors.initials: UF
authors.lastname: Rasmussen
authors.forename: J
authors.initials: J
authors.lastname: Hilsted
mesh_terms: D000042:Absorption; D000328:Adult; D019905:Benzyl Alcohol; D001592:Benzyl Alcohols / Q000737:chemistry; D001682:Biological Availability; D001786:Blood Glucose / Q000032:analysis; D002021:Buffers; D018592:Cross-Over Studies; D003718:Denmark; D005260:Female; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D007279:Injections, Subcutaneous; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011863:Radioimmunoassay; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016037:Single-Blind Method
chemical_list: D001592:Benzyl Alcohols; D001786:Blood Glucose; D002021:Buffers; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D019905:Benzyl Alcohol