The physicochemical, immunological, and biological activities of recombinant hCG are comparable to those of placental and human pregnancy urine-derived hCG. Choriogonadotropin alfa stimulates late follicular maturation and resumption of oocyte meiosis, and initiates rupture of the pre-ovulatory ovarian follicle. Choriogonadotropin alfa, the active component of Ovidrel® PreFilled Syringe, is an analogue of Luteinizing Hormone (LH) and binds to the LH/hCG receptor of the granulosa and theca cells of the ovary to effect these changes in the absence of an endogenous LH surge. In pregnancy, hCG, secreted by the placenta, maintains the viability of the corpus luteum to provide the continued secretion of estrogen and progesterone necessary to support the first trimester of pregnancy. Ovidrel® PreFilled Syringe is administered when monitoring of the patient indicates that sufficient follicular development has occurred in response to FSH treatment for ovulation induction.

Pharmacokinetics

When given by intravenous administration, the pharmacokinetic profile of Ovidrel® followed a biexponential model and was linear over a range of 25 µg to 1000 µg. Pharmacokinetic parameter estimates following SC administration of Ovidrel® 250 µg to females are presented in Table 1.

Table 1: Pharmacokinetic Parameters (mean ± SD) of r-hCG after Single-Dose Administration of Ovidrel® in Healthy Female Volunteers

Absorption

Following subcutaneous administration of Ovidrel® 250 µg, maximum serum concentration (121 ± 44 IU/L) is reached after approximately 12 to 24 hours. The mean absolute bioavailability of Ovidrel® following a single subcutaneous injection to healthy female volunteers is about 40%.

Distribution

Following intravenous administration of Ovidrel® 250 µg to healthy down- regulated female volunteers, the serum profile of hCG is described by a two- compartment model with an initial half-life of 4.5 ± 0.5 hours. The volume of the central compartment is 3.0 ± 0.5 L and the steady state volume of distribution is 5.9 ± 1.0 L.

Metabolism/Excretion

Following subcutaneous administration of Ovidrel®, hCG is eliminated from the body with a mean terminal half-life of about 29 ± 6 hours. After intravenous administration of Ovidrel® 250 µg to healthy down-regulated females, the mean terminal half-life is 26.5 ± 2.5 hours and the total body clearance is 0.29 ± 0.04 L/h. One-tenth of the dose is excreted in the urine.

Pharmacodynamics

In female subjects on oral contraception after an initial latency period, Ovidrel® induced a clear increase in androstenedione serum levels by 24 hours after dosing. Pharmacodynamic studies in females determined that the relationship of Ovidrel® pharmacokinetics to pharmacologic effect of Ovidrel® are complex and vary with the pharmacodynamic marker examined. In general pharmacologic effects are not proportional to exposure and in some cases appear to be near maximal at a 250 µg dose.

Population Pharmacokinetics and Pharmacodynamics

In patients undergoing in-vitro fertilization/embryo transfer given Ovidrel® subcutaneously to trigger ovulation, the results of a population PK/PD analysis generally supported the data obtained in healthy subjects. Pharmacokinetic parameters for Ovidrel® include a median elimination half-life of 29.2 hours, median apparent clearance (Cl/F) of 0.51 L/hr and median apparent volume of distribution (V/F) of 21.4 L.

Bioequivalence of Formulations

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