title: 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.
authors.affiliation: Department of Experimental Medicine, Ferring Pharmaceuticals A/S, Copenhagen, Denmark.
authors.forename: Håkan
authors.initials: H
authors.lastname: Olsson
authors.forename: Rikard
authors.initials: R
authors.lastname: Sandström
authors.forename: Lars
authors.initials: L
authors.lastname: Grundemar
mesh_terms: D000328:Adult; D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D018592:Cross-Over Studies; D005260:Female; D005640:Follicle Stimulating Hormone / Q000235:genetics / Q000378:metabolism / Q000493:pharmacokinetics*; D043373:Follicle Stimulating Hormone, Human / Q000235:genetics / Q000378:metabolism / Q000493:pharmacokinetics*; D006801:Humans; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000493:pharmacokinetics*; D013045:Species Specificity; D055815:Young Adult
chemical_list: C000608977:FE 999049; D043373:Follicle Stimulating Hormone, Human; D011994:Recombinant Proteins; D005640:Follicle Stimulating Hormone
keywords: bioavailability; human cell line; pharmacodynamics; pharmacokinetics; recombinant FSH