Ovidrel® PreFilled Syringe (choriogonadotropin alfa injection) - America[美国药品]

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Ovidrel® PreFilled Syringe (choriogonadotropin alfa injection)

2016-09-20 09:09:31 来源: 作者: 【大中小】浏览:357次评论:0条

SPL UNCLASSIFIED SECTION

FOR SUBCUTANEOUS USE

DESCRIPTION

Ovidrel® PreFilled Syringe (choriogonadotropin alfa injection) is a sterile liquid preparation of choriogonadotropin alfa (recombinant human Chorionic Gonadotropin, r-hCG). Choriogonadotropin alfa is a water soluble glycoprotein consisting of two non-covalently linked subunits - designated α and β - consisting of 92 and 145 amino acid residues, respectively, with carbohydrate moieties linked to ASN-52 and ASN-78 (on alpha subunit) and ASN-13, ASN-30, SER-121, SER-127, SER-132 and SER-138 (on beta subunit). The primary structure of the α - chain of r-hCG is identical to that of the α - chain of hCG, FSH and LH. The glycoform pattern of the α - subunit of r-hCG is closely comparable to urinary derived hCG (u-hCG), the differences mainly being due to the branching and sialylation extent of the oligosaccharides. The β - chain has both O- and N-glycosylation sites and its structure and glycosylation pattern are also very similar to that of u-hCG.

The production process involves expansion of genetically modified Chinese Hamster Ovary (CHO) cells from an extensively characterized cell bank into large scale cell culture processing. Choriogonadotropin alfa is secreted by the CHO cells directly into the cell culture medium that is then purified using a series of chromatographic steps. This process yields a product with a high level of purity and consistent product characteristics including glycoforms and biological activity. The biological activity of choriogonadotropin alfa is determined using the seminal vesicle weight gain test in male rats described in the "Chorionic Gonadotrophins" monograph of the European Pharmacopoeia. The in vivo biological activity of choriogonadotropin alfa has been calibrated against the third international reference preparation IS75/587 for chorionic gonadotropin.

Ovidrel® PreFilled Syringe is a sterile, liquid intended for subcutaneous (SC) injection. Each Ovidrel® PreFilled Syringe is filled with 0.515 mL containing 257.5 µg of choriogonadotropin alfa, 28.1 mg mannitol, 505 µg 85% O-phosphoric acid, 103 µg L-methionine, 51.5 µg Poloxamer 188, Sodium Hydroxide (for pH adjustment), and Water for Injection to deliver 250 µg of choriogonadotropin alfa in 0.5 mL. The pH of the solution is 6.5 to 7.5.

Therapeutic Class: Infertility

CLINICAL PHARMACOLOGY

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
	Ovidrel® 250 µg SC
Cmax: peak concentration (above baseline), tmax: time of Cmax, AUC: total area under the curve, t½: elimination half-life, F: bioavailability
* median (range)
Cmax (IU/L)	121 ± 44
tmax (h)*	24 (12-24)
AUC (h∙IU/L)	7701 ± 2101
t½ (h)	29 ± 6
F	0.4 ± 0.1

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