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Clinical Pharmacology
CLINICAL PHARMACOLOGY
Pharmacodynamics Norelgestromin is the active progestin largely responsible for the progestational activity that occurs in women following application of ORTHO EVRAŽ. Norelgestromin is also the primary active metabolite produced following oral administration of norgestimate (NGM), the progestin component of the oral contraceptive products ORTHO-CYCLENŽ and ORTHO TRI-CYCLENŽ. Text Continues Below
Combination oral contraceptives act by suppression of gonadotropins. Although the primary mechanism of this action is inhibition of ovulation, other alterations include changes in the cervical mucus (which increase the difficulty of sperm entry into the uterus) and the endometrium (which reduce the likelihood of implantation). Receptor and human sex hormone-binding globulin (SHBG) binding studies, as well as studies in animals and humans, have shown that both norgestimate and norelgestromin exhibit high progestational activity with minimal intrinsic andro-genicity90-93. Transdermally-administered norelgestromin, in combination with ethinyl estradiol, does not counteract the estrogen-induced increases in SHBG, resulting in lower levels of free
testosterone in serum compared to baseline. Pharmacokinetic studies with ORTHO EVRAŽ demonstrated consistent elimination kinetics for norelgestromin and EE with half-life values of approximately 28 hours and 17 hours, respectively. One clinical trial assessed the return of hypothalamic-pituitary-ovarian axis function post-therapy and found that FSH, LH, and Estradiol mean values, though suppressed during therapy, returned to near baseline values during the 6 weeks post therapy. Pharmacokinetics Absorption Following application of ORTHO EVRAŽ, both norelgestromin and EE rapidly appear in the serum, reach a plateau by approximately 48 hours, and are maintained at an approximate steady-state throughout the wear period. CSS concentrations for norelgestromin and EE during one week of patch wear are approximately 0.6-0.8 ng/ml and 40-50 pg/ml, respectively, and are generally consistent from all studies and application sites. These CSS concentrations are within the reference ranges for norelgestromin (0.6 to 1.2 ng/ml) and EE (25 to 75 pg/ml) established based upon the Cave concentrations observed with subjects taking ORTHO-CYCLENŽ. Page: 1 | 2 | 3 | 4 | Next >>
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