Authors: Ingrid J.M. Duijkers¹; Christine Klipping¹; Peter J. Boerrigter²; Christel S.M. Machielsen²; Joris J. de Bie²; Gerrit Voortman²

Source: Human Reproduction, Volume 17, Number 8, August 2002 , pp. 1987-1993(7)

Publisher: Oxford University Press

Abstract:

BACKGROUND: A long-acting FSH preparation has been developed by site-directed mutagenesis and gene transfer techniques. METHODS: In this open-label trial, we investigated the pharmacokinetic and pharmacodynamic properties of FSH-CTP (corifollitropin alpha, Org 36286) in healthy female volunteers. Twenty-four subjects were treated with a high-dose oral contraceptive (OC) to suppress pituitary function. A single dose of 15, 30 or 60 g FSH-CTP was injected (s.c., eight subjects per dose group) and seven of these 24 subjects were subsequently treated with a single dose of 120 g. RESULTS: Maximum serum FSH-CTP concentrations (0.42, 0.66, 1.49 and 3.27 ng/ml after administration of 15, 30, 60 and 120 g Org 36286 respectively) were reached between 36 and 48 h after injection and t<inf>1/2</inf> varied between 60 and 75 h. Dose proportionality was shown across the studied dose range, whereas t<inf>max</inf> and t<inf>1/2</inf> were dose independent. In most subjects follicular growth was observed; the number and maximum diameter of the follicles increased with the dose. Follicles with a diameter 8.0 mm were observed only in the 60 and 120 g dose groups, diameters between 12.0 and 15.9 mm occurred only in the 120 g group. Serum LH and 17-oestradiol levels remained low due to profound pituitary suppression whereas inhibin-B levels increased with dose. Maximum mean inhibin-B levels were 30.4, 322.7 and 1059.3 pg/ml in the 30, 60 and 120 g dose group respectively. The preparation was safe and well tolerated, and no FSH-CTP antibody formation was observed. CONCLUSIONS: The pharmacokinetics of FSH-CTP were shown to be proportional with the dose. The elimination half-life was approximately two times longer than that of rFSH. A single dose of FSH-CTP was shown to be safe and able to induce multiple follicular growth accompanied by a dose-dependent rise in serum inhibin-B concentrations.

Keywords: FSH-CTP; infertility; long-acting; pharmacodynamics; pharmacokinetics

Document Type: Research article

Affiliations: 1: Dinox Medical Investigations, Groenewoudseweg 317, 6524 TX, Nijmegen and 2: N.V. Organon, Molenstraat 110, P.O.Box 20, 5340 BH, Oss, The Netherlands

Publication date: 2002-08-01

More about this publication?

• Human Reproduction features full-length, peer-reviewed papers reporting original research, clinical case histories, as well as opinions and debates on topical issues. Papers published cover the scientific and medical aspects of reproductive physiology and pathology, endocrinology, andrology, gonad function, gametogenesis, fertilization, embryo development, implantation, pregnancy, genetics, genetic diagnosis, oncology, infectious disease, surgery, contraception, infertility treatment, psychology, ethics and social issues. The highest scientific and editorial standard is maintained throughout the journal along with a rapid rate of publication.

Related content

• In this: publication
• By this: publisher
• In this Subject: Anatomy & Physiology ,  Obstetrics & Gynecology
• By this author: Ingrid J.M. Duijkers ;  Christine Klipping ;  Peter J. Boerrigter ;  Christel S.M. Machielsen ;  Joris J. de Bie ;  Gerrit Voortman

Website © Publishing Technology. Article copyright remains with the publisher, society or author(s) as specified within the article.

• Terms and conditions
• Privacy policy
• Information for advertisers