Different pharmacokinetic and pharmacodynamic properties of recombinant follicle-stimulating hormone (rFSH) derived from a human cell line compared with rFSH from a non-human cell line

Abstract

Pharmacokinetic and pharmacodynamic properties of a novel recombinant follicle-stimulating hormone (rFSH) preparation (FE 999049), expressed by a human cell line (PER.C6), was compared with an rFSH preparation (follitropin α) expressed by a Chinese hamster ovary (CHO) cell line in healthy pituitary-suppressed women. Following single intravenous administration of 225 IU (Steelman-Pohley assay), the clearance was lower, 0.31 versus 0.44 L/h, for FE 999049 than for follitropin α. Likewise, the apparent clearance after repeated daily subcutaneous administrations was lower, 0.58 versus 0.99 L/h, and AUC and C(max) higher, 1.7- and 1.6-fold. The absolute bioavailability after a single subcutaneous dose of 450 IU was similar for both preparations, 60-65%. After repeated subcutaneous administration the elimination half-life was approximately 30 and 24 hours for FE 999049 and follitropin α. The ovarian responses by number of follicles and serum concentrations of inhibin B and estradiol, were higher with FE 999049 than with follitropin α, AUC and C(max) for the two latter being >1.6-fold greater with FE 999049 than with follitropin α. These results indicate that administration of equal doses of FE 999049, expressed in a human cell line, and follitropin α, expressed in a CHO cell line, display different pharmacokinetic and pharmacodynamic properties in humans.

Keywords: bioavailability; human cell line; pharmacodynamics; pharmacokinetics; recombinant FSH.