Bioequivalence of subcutaneous injections of recombinant human follicle stimulating hormone (Puregon(R)) by Pen-injector and syringe.
A randomized, single-centre, cross-over study was designed to compare the bioavailability of two pharmaceutical formulations of recombinant human follicle stimulating hormone (recFSH; Puregon(R)): (i) a dissolved cake injected by a normal syringe; and (ii) a ready-for-use solution injected using a device referred to as Puregon(R)Pen. Twenty-two healthy female volunteers underwent one of two administration sequences: Puregon(R)Pen/syringe or syringe/Puregon(R)Pen, by which they received a single subcutaneous dose of recFSH (150 IU). Endogenous gonadotrophin production had been previously suppressed using an oral contraceptive (Lyndiol(R)). Pharmacokinetic parameters characterizing rate [peak concentration (Cmax) and time of peak concentration (tmax)] and extent [area under the curve (AUC) and clearance (CL)] of absorption were obtained from 20 subjects. After injection with both formulations, serum FSH concentrations reached a peak of 3.4 IU/l at 13 h after injection. The elimination half-life was approximately 34 h, irrespective of formulation. A difference of approximately 18% was found between serum FSH concentrations obtained using the two formulations, which was caused by differences between the anticipated and the actual volume injected with the normal syringe. After correction for injection losses by weighing the amount injected with a normal syringe, the two formulations were found to be bioequivalent with respect to Cmax, AUC and CL. For tmax, bioequivalence could not be proven due to high intra-subject variability and broad absorption peaks of FSH. Both methods were well tolerated, local reactions being generally mild and short-lived.
Scientific Development Group, NV Organon, PO Box 20, 5340 BH Oss Centre for Human Drug Research, Zernikedreef 10, 2333 CL Leiden, The Netherlands.
G
G
Voortman
J
J
van de Post
R C
RC
Schoemaker
J M
JM
van Gerven
D000293:Adolescent; D000328:Adult; D001682:Biological Availability; D018592:Cross-Over Studies; D005260:Female; D005640:Follicle Stimulating Hormone / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D043373:Follicle Stimulating Hormone, Human; D006801:Humans; D007279:Injections, Subcutaneous / Q000009:adverse effects / Q000295:instrumentation; D010062:Ovulation Induction / Q000379:methods; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D012646:Self Administration / Q000009:adverse effects / Q000379:methods; D013594:Syringes; D013810:Therapeutic Equivalency
D043373:Follicle Stimulating Hormone, Human; D011994:Recombinant Proteins; D005640:Follicle Stimulating Hormone