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
(2014) In Journal of Clinical Pharmacology 54(11). p.1299-1307- 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... (More)
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.
(Less)
- author
- Olsson, Håkan ; Sandström, Rikard and Grundemar, Lars LU
- publishing date
- 2014-11
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Adult, Animals, CHO Cells, Cell Line, Cricetinae, Cricetulus, Cross-Over Studies, Female, Follicle Stimulating Hormone/genetics, Follicle Stimulating Hormone, Human/genetics, Humans, Recombinant Proteins/genetics, Species Specificity, Young Adult
- in
- Journal of Clinical Pharmacology
- volume
- 54
- issue
- 11
- pages
- 1299 - 1307
- publisher
- SAGE Publications
- external identifiers
-
- pmid:24800998
- scopus:84921982584
- ISSN
- 0091-2700
- DOI
- 10.1002/jcph.328
- language
- English
- LU publication?
- no
- additional info
- © 2014, The American College of Clinical Pharmacology.
- id
- c00305cb-4e9b-40c7-8d8c-33e891b9ffec
- date added to LUP
- 2019-09-03 13:00:10
- date last changed
- 2024-07-25 04:28:42
@article{c00305cb-4e9b-40c7-8d8c-33e891b9ffec, abstract = {{<p>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.</p>}}, author = {{Olsson, Håkan and Sandström, Rikard and Grundemar, Lars}}, issn = {{0091-2700}}, keywords = {{Adult; Animals; CHO Cells; Cell Line; Cricetinae; Cricetulus; Cross-Over Studies; Female; Follicle Stimulating Hormone/genetics; Follicle Stimulating Hormone, Human/genetics; Humans; Recombinant Proteins/genetics; Species Specificity; Young Adult}}, language = {{eng}}, number = {{11}}, pages = {{1299--1307}}, publisher = {{SAGE Publications}}, series = {{Journal of Clinical Pharmacology}}, 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}}, url = {{http://dx.doi.org/10.1002/jcph.328}}, doi = {{10.1002/jcph.328}}, volume = {{54}}, year = {{2014}}, }