Assessment of the biopotency of follitropin alfa and lutropin alfa combined in one injection: a comparative trial in Sprague-Dawley rats.
BACKGROUND
The current study was designed to determine if follitropin alfa (recombinant human follicle-stimulating hormone; r-hFSH) and lutropin alfa (recombinant human luteinizing hormone; r-hLH) biopotencies were unchanged by reconstituting in sterile water for injection and mixing prior to injection.


METHODS
The biopotencies of r-hFSH and r-hLH were determined following injection of female Sprague-Dawley rats with a mixture of follitropin alfa revised formulation female (RFF) and lutropin alfa (1:1, r-hFSH:r-hLH). Biopotencies of follitropin alfa RFF and lutropin alfa were measured using ovarian weight and ascorbic acid depletion assays, respectively, and compared with a reference standard. Stock mixtures of follitropin alfa RFF and lutropin alfa (1:1) were prepared within 1 h prior to each respective assay's injection and stored at 6 +/- 2 degrees C. Separate low dose (follitropin alfa RFF 1.5 IU/rat, lutropin alfa 2 IU/rat) and high dose (follitropin alfa RFF 3 IU/rat, lutropin alfa 8 IU/rat) treatments were prepared from stock mixtures or individual solutions by diluting with 0.22% bovine serum albumin saline solution and injected within 1 h of preparation. The main outcome measures were ovarian weight and ovarian ascorbic acid depletion.


RESULTS
FSH bioactivities were similar (p > 0.10) between the individual follitropin alfa RFF test solution (84.2 IU) and follitropin alfa RFF/lutropin alfa (87.6 IU) mixtures prepared within 1 h of injection and stored at 6 +/- 2 degrees C. LH bioactivities were similar (p > 0.10) between lutropin alfa (94.7 IU) test solution and lutropin alfa/follitropin alfa RFF (85.3 IU) mixtures prepared within 1 h of injection and stored at 6 +/- 2 degrees C for not more than 1 h prior to injection.


CONCLUSIONS
Mixing follitropin alfa RFF and lutropin alfa did not alter the bioactivity of either FSH or LH.
Alper
Michael
M
EMD Serono, Inc, (an affiliate of Merck KGaA, Darmstadt, Germany), Rockland, MA, USA. michael.alper@bostonivf.com
Meyer
Randal
R
Dekkers
Chris
C
Ezcurra
Diego
D
Schertz
Joan
J
Kelly
Eduardo
E
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D004338:Drug Combinations; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism / Q000494:pharmacology*; D015292:Glycoprotein Hormones, alpha Subunit / Q000378:metabolism / Q000494:pharmacology*; D007267:Injections; D007986:Luteinizing Hormone / Q000378:metabolism / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000033:anatomy & histology / Q000187:drug effects; D010969:Plastics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013594:Syringes
D004338:Drug Combinations; D015292:Glycoprotein Hormones, alpha Subunit; D010969:Plastics; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D001205:Ascorbic Acid