OBJECTIVE: To assess and compare the pharmacokinetics of recombinant human FSH with those of a reference preparation of urinary human FSH. DESIGN: Urinary human FSH and recombinant human FSH (Metrodin and Gonal-F; Laboratoires Serono, Aubonne, Switzerland) were administered in a balanced, random order, crossover sequence as a single i.v. dose of 150 or 300 IU separated by 1 week of washout to 12 pituitary down-regulated, healthy female volunteers. Serum FSH concentrations were measured by an immunoradiometric assay (IRMA) and by an in vitro rat granulosa cell aromatase bioassay. Urine FSH concentrations were measured by IRMA. RESULTS: The mean concentration-time profiles after 150 IU of urinary human FSH and recombinant human FSH were superimposed, and the mean profile after 300 IU of recombinant human FSH was double that of the 150 IU dose. The data for both FSH preparations were well described by a biexponential equation. Total clearance of the preparations was comparable, judging from immunoassay and bioassay data (0.5 and 0.15 L/h, respectively). Based on the immunoassay, renal clearance of urinary human FSH was 0.1 L/h, whereas for recombinant human FSH it was slightly lower at 0.07 L/h, indicating that less than one fifth of the administered dose was excreted in the urine. Immunoassay showed that the two preparations were similar in terms of initial and terminal half-lives (2 and 17 hours, respectively). The volumes of distribution at steady state (11 L) were similar. The results of the in vitro bioassay confirmed this pharmacokinetic analysis. Just after i.v. administration, an initial decrease in the serum bioassay:immunoassay ratio was observed because of dilution of urinary human FSH or of recombinant human FSH in the residual endogenous FSH pool. Then the ratio increased progressively with time, suggesting either metabolic selection or activation of both types of injected human FSH toward forms with greater in vitro bioactivity. The bioassay:immunoassay ratio returned to baseline by day 7. CONCLUSION: The results obtained in this study indicate that the following [1] the pharmacokinetic characteristics of recombinant human FSH are similar to those of urinary human FSH; [2] the terminal half-life of human FSH is approximately 1 day; [3] after a single i.v. injection of human FSH a progressive increase in FSH bioassay: immunoassay ratio is observed; and [4] clinical use of recombinant human FSH could follow protocols and treatment regimens currently applied to urinary human FSH.
RCT Entities:
OBJECTIVE: To assess and compare the pharmacokinetics of recombinant human FSH with those of a reference preparation of urinary human FSH. DESIGN: Urinary human FSH and recombinant human FSH (Metrodin and Gonal-F; Laboratoires Serono, Aubonne, Switzerland) were administered in a balanced, random order, crossover sequence as a single i.v. dose of 150 or 300 IU separated by 1 week of washout to 12 pituitary down-regulated, healthy female volunteers. Serum FSH concentrations were measured by an immunoradiometric assay (IRMA) and by an in vitro rat granulosa cell aromatase bioassay. Urine FSH concentrations were measured by IRMA. RESULTS: The mean concentration-time profiles after 150 IU of urinary human FSH and recombinant human FSH were superimposed, and the mean profile after 300 IU of recombinant human FSH was double that of the 150 IU dose. The data for both FSH preparations were well described by a biexponential equation. Total clearance of the preparations was comparable, judging from immunoassay and bioassay data (0.5 and 0.15 L/h, respectively). Based on the immunoassay, renal clearance of urinary human FSH was 0.1 L/h, whereas for recombinant human FSH it was slightly lower at 0.07 L/h, indicating that less than one fifth of the administered dose was excreted in the urine. Immunoassay showed that the two preparations were similar in terms of initial and terminal half-lives (2 and 17 hours, respectively). The volumes of distribution at steady state (11 L) were similar. The results of the in vitro bioassay confirmed this pharmacokinetic analysis. Just after i.v. administration, an initial decrease in the serum bioassay:immunoassay ratio was observed because of dilution of urinary human FSH or of recombinant human FSH in the residual endogenous FSH pool. Then the ratio increased progressively with time, suggesting either metabolic selection or activation of both types of injected human FSH toward forms with greater in vitro bioactivity. The bioassay:immunoassay ratio returned to baseline by day 7. CONCLUSION: The results obtained in this study indicate that the following [1] the pharmacokinetic characteristics of recombinant human FSH are similar to those of urinary human FSH; [2] the terminal half-life of human FSH is approximately 1 day; [3] after a single i.v. injection of human FSH a progressive increase in FSH bioassay: immunoassay ratio is observed; and [4] clinical use of recombinant human FSH could follow protocols and treatment regimens currently applied to urinary human FSH.