Comparative pharmacokinetics of two urinary human follicle stimulating hormone preparations in healthy female and male volunteers

Abstract

These studies were designed to compare the pharmacokinetic characteristics of a very highly purified urinary human follicle stimulating hormone (FSH-HP) preparation (sp. act. approximately 9000 IU FSH/mg of protein), Metrodin HP, with a standard urinary FSH preparation Metrodin (FSH). The two preparations were administered in a balanced, random-order, cross-over sequence as single doses of 150 IU, separated by 1 week of washout to 12 female volunteers by i.v. injection and to 12 male volunteers by i.m. and s.c. routes. FSH concentrations were measured by immunoradiometric assay and by an in-vitro rat granulosa cell aromatase bioassay. After an i.v. bolus, the pharmacokinetics of the two FSH preparations were identical. Total clearance was 0.5 and 0.15 l/h respectively for immunoassay and bioassay data. Immunoassay showed that the two preparations were similar for renal clearance (0.1 l/h), volumes of distribution at steady state (9 l), distribution and terminal half-lives (2 and 17 h, respectively). After parenteral administrations, the absorption half-life of FSH was approximately 3 h and the apparent terminal half-life was approximately 1.5 days. Both preparations had relative bioavailabilities close to 100% for i.m. and s.c. administrations. Immunopurification, which results in a very highly purified FSH-HP, does not modify the pharmacokinetic properties of FSH. This study also confirmed that s.c. and i.m. doses of FSH-HP are equivalent from the pharmacokinetic and pharmacodynamic points of view.