Bioequivalence of Two Recombinant Human Growth Hormones in Healthy Male Volunteers after Subcutaneous Administration

The bioequivalence of recombinant human growth hormone (rhGH) (somatropin) and its N-methionyl variant (Met-hGH) [Protropin((R)) (somatrem for injection)] was determined in 42 healthy male volunteers (n = 21 per treatment) who were randomized to receive either protein by subcutaneous administration of 0.1 mg kg(minus sign1). Serum samples were collected over 24 h after the injection, and the concentration of human growth hormone (hGH) were determined by an immunoradiometric assay. Bioequivalence of the two proteins was assessed by determining whether the 90% confidence limits for the ratio of geometric means using logarithmically transformed AUC and C(max) parameters (log(10)AUC(0--24), log(10)AUC(0--infty infinity), and log(10)C(max)) were within the 80--125% range. The bioequivalence of the two treatments was also tested by calculating a bioequivalance index (xi(2)) that measured the difference between the two mean concentration-time profiles. The 90% confidence intervals for the ratios of the geometric means for AUC were within the prescribed 80--125% range for bioequivalence. The upper limit of the 90% confidence interval for the ratio of the geometric means for C(max) fell slightly outside the 125% criterion even though the geometric mean itself, 106.6%, was very close to the ideal of 100%. There was a larger standard error associated with C(max) than with the AUCs, and this marginally larger confidence limit for C(max) resulted more from the variance among the subject than to the difference in the means. In fact, the bioequivalence index, xi(2), was 0.075, indicating that the mean curves after rhGH and Met-hGH are essentially superimposable.