Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Gonadotrophins
ATC code: G03G A02
Menotrophin (Human Menopausal Gonadotrophin, HMG) is a gonadotrophin extracted from the urine of post menopausal women. It has both luteinising hormone and follicle stimulating hormone activity in a 1:1 ratio. Human Chorionic Gonadotrophin (hCG), a naturally occurring hormone in postmenopausal urine, is present in MENOPUR and is the main contributor of the LH activity.
Menotrophin (HMG) directly affects the ovaries and the testes. HMG has a gametropic and steroidogenic effect.
In the ovaries, the FSH-component in HMG induces an increase in the number of growing follicles and stimulates their development. FSH increases the production of oestradiol in the granulosa cells by aromatising androgens that originate in the Theca cells under the influence of the LH-component.
Follicular growth can be stimulated by FSH in the total absence of LH, but the resulting follicles develop abnormally and are associated with low oestradiol levels and inability to luteinize to a normal ovulatory stimulus.
In line with the action of LH activity in enhancing stereoidogenesis, oestradiol levels associated with treatment with MENOPUR are higher than with recombinant FSH preparations in downregulated IVF/ICSI cycles. This issue should be considered when monitoring patient´s response based on oestradiol levels. In the testes, FSH induces the transformation of premature to mature Sertoli cells. It mainly causes the maturation of the seminal canals and the development of the spermatozoa. However, a high concentration of androgens within the testes is necessary and can be attained by a prior treatment using hCG.

Pharmacokinetic Properties

5.2 Pharmacokinetic properties
The pharmacokinetics of Menotrophin following intramuscular or subcutaneous administration shows great interindividual variability. After 7 days of repeated dosing with 150 IU MENOPUR in downregulated healthy female volunteers, maximum plasma FSH concentrations (baseline-corrected) (mean ± SD) were 8.9 ± 3.5 IU/L and 8.5 ± 3.2 IU/L for the SC and IM administration, respectively. The area under the curve (AUCT) of FSH concentration was (mean ± SD) 180 ± 77 h.IU/L and 166 ± 67 h.IU/L for SC and IM administration, respectively.Maximum FSH concentrations were reached within 7 hours for both routes of administration. After repeated administration, FSH was eliminated with a half- life (mean ± SD) of 30 ± 11 hours and 27 ± 9 hours for the SC and IM administration, respectively. Although the individual LH concentration versus time curves show an increase in the LH concentration after dosing with MENOPUR, the data available were too sparse to be subjected to a pharmacokinetic analysis.
Menotrophin is excreted primarily via the kidneys.
The pharmacokinetics of MENOPUR in patients with renal or hepatic impairment has not been investigated.