ASSESSMENT OF BIOEQUIVALENCE AFTER SUBCUTANEOUS AND INTRAMUSCULAR ADMINISTRATION OF URINARY GONADOTROPINS

The objective was to demonstrate bioequivalence between s.c. and i.m. administration of Humegon(R) (FSH/LH ratio 1:1) and Normegon(R) (FSH/L H ratio 3:1), In two randomized, single-centre, cross-over studies, 18 healthy volunteers on each formulation were assigned to one of the tw o administration sequences, Subjects were given single doses of one of the above gonadotrophins after endogenous gonadotrophin production ha d first been suppressed using high-dose oral contraceptive, Subsequent ly, rate (C-max, t(max)) and extent (AUC) of absorption of follicle st imulating hormone (FSH) and luteinizing hormone (LH) were determined f or 14 days, For C-max, and AUC, analysis of variance (ANOVA) was perfo rmed on log-transformed data and for t(max) ANOVA was performed on ran ks, Intramuscular and s.c. injections of Humegon were bioequivalent wi th 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 wi th respect to the C-max of FSH. For t(max) of FSH as web as for most L H variables of both preparations, bioequivalence could not be be prove n due to the high intra- and interindividual variability and/or concen trations being close to the detection limit. Thus, the main pharmacoki netic FSH variables after i.m. and s.c. administration of Humegon and Normegon were bioequivalent.