The bioequivalence of liquid and freeze-dried formulations of recombinant human chorionic gonadotrophin.
OBJECTIVE
To compare the bioavailability and tolerability of liquid and freeze-dried formulations of recombinant human chorionic gonadotrophin (r-hCG).


METHODS
In an open-label, randomised, single-centre, Phase I study, healthy adult volunteers (18-50 years of age) received single injections of r-hCG 250 microg from reconstituted freeze-dried (1.0 mL of 250 microg/mL) and liquid (0.5 mL of 250 microg/0.5 mL) formulations in random order, separated by a 10-day wash-out period. Pharmacokinetics (C(max), AUC, AUC(last), t(max)) and local and systemic tolerability were assessed.


RESULTS
Pharmacokinetic properties of the two formulations were very similar, with mean C(max) 125 mIU/mL (liquid formulation) vs 129 mIU/mL (freeze-dried formulation), mean AUC 10,350 mIU.h/mL vs 10,480 mIU(.)h/mL, mean AUC(last) 10,050 mIU.h/mL vs 10,210 mIU.h/mL, and median t(max) 20 vs 24h. The 90% confidence intervals of the ratios of the treatment means for C(max), AUC and AUC(last) all fell within the pre-defined FDA acceptance range of 0.8-1.25, demonstrating the bioequivalence of the two formulations. Both formulations were equally well tolerated; the most frequent adverse events were headache and nausea.


CONCLUSIONS
The liquid formulation of r-hCG was shown to be bioequivalent to the freeze-dried formulation, with no clinically significant differences in tolerability. The liquid formulation of r-hCG can be expected to provide the same efficacy and tolerability as the freeze-dried formulation when used to trigger final follicular maturation in women undergoing therapies for assisted reproduction, together with a greater convenience of use.
van der Merwe
R
R
Bourn Hall Clinic, Cambridge, UK.
Lugan
I
I
Lecuelle
H
H
Papasouliotis
O
O
Buraglio
M
M
D000328:Adult; D001682:Biological Availability; D006063:Chorionic Gonadotropin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004304:Dosage Forms; D005260:Female; D005612:Freeze Drying; D006801:Humans; D008297:Male; D019999:Pharmaceutical Solutions; D013810:Therapeutic Equivalency; D016896:Treatment Outcome
D006063:Chorionic Gonadotropin; D004304:Dosage Forms; D019999:Pharmaceutical Solutions