Bioavailability of Recombinant Human Growth Hormone in Different Concentrations and Formulations

: 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 (∼1.37 mg/ml), (2) 5.9 IU/ml in a phosphate buffer dissolved in 1.5% benzyl alcohol (∼2 mg/ml) and (3) 11.7 IU/ml in a phosphate buffer dissolved in 1.5% benzyl alcohol (∼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 Conventional growth hormone‐therapy was withdrawn 2 days before each study period.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.