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Oral Contraception

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 binding studies, as well as studies in animals and humans, have shown that norgestimate and 17-deacetyl norgestimate, the major serum metabolite, combine high progestational activity with minimal intrinsic androgenicity.^90-93 Norgestimate, in combination with ethinyl estradiol, does not counteract the estrogen-induced increases in sex hormone binding globulin (SHBG), resulting in lower serum testosterone.^90,91,94

Acne

Acne is a skin condition with a multifactorial etiology. The combination of ethinyl estradiol and norgestimate may increase sex hormone binding globulin (SHBG) and decrease free testosterone resulting in a decrease in the severity of facial acne in otherwise healthy women with this skin condition.

Norgestimate and ethinyl estradiol are well absorbed following oral administration of Sprintec (norgestimate and ethinyl estradiol tablets) . On the average, peak serum concentrations of norgestimate and ethinyl estradiol are observed within two hours (0.5-2.0 hr for norgestimate and 0.75-3.0 hr for ethinyl estradiol) after administration followed by a rapid decline due to distribution and elimination. Although norgestimate serum concentrations following single or multiple dosing were generally below assay detection within 5 hours, a major norgestimate serum metabolite, 17-deacetyl norgestimate, (which exhibits a serum half-life ranging from 12 to 30 hours) appears rapidly in serum with concentrations greatly exceeding that of norgestimate. The 17-deacetylated metabolite is pharmacologically active and the pharmacologic profile is similar to that of norgestimate. The elimination half-life of ethinyl estradiol ranged from approximately 6 to 14 hours.

Both norgestimate and ethinyl estradiol are extensively metabolized and eliminated by renal and fecal pathways. Following administration of ¹⁴C-norgestimate, 47% (45-49%) and 37% (16-49%) of the administered radioactivity was eliminated in the urine and feces, respectively. Unchanged norgestimate was not detected in the urine. In addition to 17-deacetyl norgestimate, a number of metabolites of norgestimate have been identified in human urine following administration of radiolabeled norgestimate. These include 18, 19-Dinor-17-pregn-4-en-20-yn-3-one, 17-hydroxy-13-ethyl,(17α)-(-);18,19-Dinor-5β-17-pregnan-20-yn,3α,17β-dihydroxy-13-ethyl,(17α), various hydroxy-lated metabolites and conjugates of these metabolites. Ethinyl estradiol is metabolized to various hydroxylated products and their glucuronide and sulfate conjugates.

REFERENCES

91. Chapdelaine A, Desmaris J-L, Derman RJ. Clinical evidence of minimal androgenic activity of norgestimate. Int J Fertil 1989; 34(51):347-352.

92. Phillips A, Demarest K, Hahn DW, Wong F, McGuire JL. Progestational and androgenic receptor binding affinities and in vivo activities of norgestimate and other progestins. Contraception 1989; 41(4):399-409.

93. Phillips A, Hahn DW, Klimek S, McGuire JL. A comparison of the potencies and activities of progestogens used in contraceptives. Contraception 1987:36(2):181-192.

94. Janaud A, Rouffy J, Upmalis D, Dain M-P. A comparison study of lipid and androgen metabolism with triphasic oral contraceptive formulations containing norgestimate or levonorgestrel. Acta Obstet Gynecol Scand 1992; 156 (Supplement):34-38.

Last reviewed on RxList: 12/10/2008
This monograph has been modified to include the generic and brand name in many instances.