Absorption kinetics of two highly concentrated preparations of growth hormone: 12 IU/ml compared to 56 IU/ml

The purpose of this study was to compare the relative bioavailability of two highly concentrated (12 IU/ml versus 56 IU/ml) formulations of biosynthetic human growth hormone administered subcutaneously. After pretreatment with growth hormone for at least four weeks, nine growth hormone deficient patients with a mean age of 26.2 years (range 17-43) were studied two times in a randomized design, the two studies being separated by at least one week. At the start of each study period (7 p.m.), growth hormone was injected subcutaneously in a dosage of 3 IU/m2. The 12 IU/ml preparation of growth hormone was administered on one occasion, and the 56 IU/ml preparation on the other. Serum profiles of growth hormone were monitored by frequent measurements for 24 hr. Bioavailability and absorption dynamics were evaluated by the absorption fraction, F56 IU/12 IU, calculated from the mean integrated levels (AUC) of growth hormone, and the observed time, Tmax, to reach maximum concentration, Cmax. Levels of serum IGF-I, IGFBP-3, insulin and blood glucose were measured to study the short term metabolic effects of growth hormone. The absorption fraction, F (S.D.) was 1.034 (0.163). The 90% confidence interval was 0.934-1.144, which is included in the interval 0.8-1.25, implying that the two preparations are bioequivalent. Neither AUC (P = 0.90), Cmax (p = 0.47) or Tmax (P = 0.86) for the two formulations of growth hormone were significantly different. Similar levels of serum IGF-I, IGFBP-3, insulin and blood glucose were obtained.(ABSTRACT TRUNCATED AT 250 WORDS)