Assessment of bioequivalence after subcutaneous and intramuscular administration of urinary gonadotrophins

Abstract

The objective was to demonstrate bioequivalence between s.c. and i.m. administration of Humegon® (FSH/LH ratio 1:1) and Normegon® (FSH/LH ratio 3:1). In two randomized, single-centre, cross-over studies, 18 healthy volunteers on each formulation were assigned to one of the two administration sequences. Subjects were given single doses of one of the above gonadotrophins after endogenous gonadotrophin production had first been suppressed using high-dose oral contraceptive, Subsequently, rate (C(max), t(max)) and extent (AUC) of absorption of follicle stimulating hormone (FSH) and luteinizing hormone (LH) were determined for 14 days, For C(max) and AUC, analysis of variance (ANOVA) was performed on log-transformed data and for t(max) ANOVA was performed on ranks. Intramuscular and s.c. injections of Humegon were bioequivalent with respect to the main pharmacokinetic parameters, being AUC and C(max) of FSH absorption. Intramuscular and s.c. injections of Normegon were bioequivalent with respect to the AUC of FSH and not bioequivalent with respect to the C(max) of FSH. For t(max) of FSH as well as for most LH variables of both preparations, bioequivalence could not be be proven due to the high intra- and interindividual variability and/or concentrations being close to the detection limit. Thus, the main pharmacokinetic FSH variables after i.m. and s.c. administration of Humegon and Normegon were bioequivalent.