Human follicle stimulating hormone in women
Follicle stimulating hormone (FSH) is one of the key hormones regulating reproductive function in both genders. FSH, a heterodimeric glycoprotein, is produced in the anterior pituitary gland and then secreted into the general circulation. In the female it stimulates growth and maturation of ovarian follicles; in males it promotes spermatogenesis. One indication for human FSH is the stimulation of multiple follicular development in ovulatory patients undertaking in vitro fertilisation and embryo transfer (IVF-ET). Currently available human FSH preparations are extracted from the urine of postmenopausal women and have low specific activity due to the presence of non-specific co-purified urinary proteins. Biotechnology has made possible production of a high specific activity recombinant human FSH preparation through an in vitro process independent of urine collection (recombinant-human FSH).
The primary objective of the present analysis was to characterize the population pharmacokinetics of intramuscular (i.m.) urinary-human FSH (u-hFSH) and subcutaneous (s.c.) recombinant-human FSH (r-hFSH) in a large group of patients undergoing IVF-ET, and to assess which covariates, if any, influence the variability of FSH pharmacokinetics. The study was a multicentre, randomized, open, parallel group study to compare the efficacy and safety of r-hFSH and u-hFSH. The study was designed with the intention of employing a population approach to the data analysis and thus only sparse numbers of blood samples were taken from each patient during the course of the study.
Administration of an endogenous substance in a pharmacokinetic study gives rise to certain problems that are not normally present with xenobiotic drugs. The resulting plasma concentrations are the result of both endogenous and exogenous parts and these must be distinguished before the pharmacokinetics of the exogenously administered substance can be correctly characterized. The information about many of the model parameters is sparse and therefore the population approach has an advantage over traditional pharmacokinetic methods since it pools the available information across many subjects.
Preliminary analysis of the sparse data indicated that absorption was the rate limiting step for the pharmacokinetics of both u-hFSH and r-hFSH. Since the sampling design in the study did not allow determination of the elimination half-life and volume/bioavailability (VÂ /F ), previously collected experimental data of u-hFSH and r-hFSH were made available. Additional information about the absorption and disposition of u-hFSH and r-hFSH was gained by using deconvolution techniques in independent analyses of the intensively sampled data sets. This information was then utilised in the population analysis.
Filed under: Clinical Pharmacology