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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

Olsson, Håkan; Sandström, Rikard and Grundemar, Lars LU (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.

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author
publishing date
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 Inc.
external identifiers
  • scopus:84921982584
ISSN
0091-2700
DOI
10.1002/jcph.328
language
English
LU publication?
no
id
c00305cb-4e9b-40c7-8d8c-33e891b9ffec
date added to LUP
2019-09-03 13:00:10
date last changed
2019-10-15 07:12:22
@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 &gt;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},
  keyword      = {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 Inc.},
  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},
  volume       = {54},
  year         = {2014},
}