Assessment of bioequivalence after subcutaneous and intramuscular administration of urinary gonadotrophins

The objective was to demonstrate bioequivalence between s.c. and i.m.administration of Humegon (FSH/LH ratio 1:1) and Normegon (FSH/LH ratio3:1). In two randomized, single-centre, cross-over studies, 18 healthyvolunteers on each formulation were assigned to one of the twoadministration sequences. Subjects were given single doses of one of theabove gonadotrophins after endogenous gonadotrophin production had firstbeen suppressed using high-dose oral contraceptive. Subsequently, rate(Cmax, tmax) and extent (AUC) of absorption of follicle stimulating hormone(FSH) and luteinizing hormone (LH) were determined for 14 days. For Cmaxand AUC, analysis of variance (ANOVA) was performed on log-transformed dataand for tmax ANOVA was performed on ranks. Intramuscular and s.c.injections of Humegon were bioequivalent with respect to the mainpharmacokinetic parameters, being AUC and Cmax of FSH absorption.Intramuscular and s.c. injections of Normegon were bioequivalent withrespect to the AUC of FSH and not bioequivalent with respect to the Cmax ofFSH. For tmax of FSH as well as for most LH variables of both preparations,bioequivalence could not be proven due to the high intra- andinterindividual variability and/or concentrations being close to thedetection limit. Thus, the main pharmacokinetic FSH variables after i.m.and s.c. administration of Humegon and Normegon were bioequivalent.