BIOAVAILABILITY OF RECOMBINANT HUMAN GROWTH-HORMONE IN DIFFERENT CONCENTRATIONS AND FORMULATIONS

Whether the bioavailability of growth hormone depends on the concentra tion or formulation of the preparation was evaluated in 18 growth horm one-deficient patients. The design was a single-blinded, randomized cr oss-over study, where the patients were given a single, fixed dose sub cutaneous injection of growth homrone (3 IU/m(2)) of 3 different prepa rations: (1) 4 IU/ml in a bicarbonate buffer dissolved in 0.9% benzyl alcohol (approximate to 1.37 mg/ml), (2) 5.9 IU/ml in a phosphate buff er dissolved in 1.5% benzyl alcohol (approximate to 2 mg/ml) and (3) 1 1.7 IU/ml in a phosphate buffer dissolved in 1.5% benzyl alcohol (appr oximate to 4 mg/ml). Conventional growth hormone-therapy was withdrawn 2 days before each study period. Blood samples were drawn over a 24-h r period and assessed for growth hormone, serum insulin-like growth fa ctor I (IGF-I), insulin and glucose. The geometric mean values (+/-geo metric S.D.) of the relative absorption fractions were F-5.9 IU/4 IU=A UC(5.9 IU)/AUC(4 IU)=(+/-1.139) (P=0.66), F-11.7 IU/AUC(4 IU)=AUC(11.7 IU)/AUC(4 IU) (1.14+/-1.21) (P=0.009) and F-11.7 IU/5.9=AUC(11.7 IU)/ AUC(5.9 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 relat ive observed maximum concentration, C-max was for C-max 5.9 IU/C-max 4 IU=1.04 (+/-1.19) (P=0.32), C-max 11.7 IU/C-max 4 IU=1.24 (+/-1.21) ( P=0.0002) and C-max 11.7 IU/C-max 5.9 IU=1.19(+/-1.29) (P=0.012). The median and the range values for the observed time to reach C-max was t (max 5.9 IU)/t(max 4 IU)=0.63 (0.04-1.00), t(max 11.7 IU)/t(max 4 IU)= 0.59 (0.06-1.0) and t(max 11.7 IU)/t(max 5.9 IU)=0.90 (0.51-18.00). Th ere were no significant differences in IGF-I, glucose and insulin prof iles. Based on the upper limits of the 90% confidence intervals for re lative AUC's the conclusion is that the three different preparations w ere bioequivalent.