"Despite the potential for adverse maternal and fetal outcomes, contraceptive use in women with certain medical conditions is suboptimal, according to a new study.
Steven W. Champaloux, PhD, MPH, a scientist in the Division of Reproduc"...
Mechanism Of Action
- Oral Contraception
COCs lower the risk of becoming pregnant primarily by suppressing ovulation. Other possible mechanisms may include cervical mucus changes that inhibit sperm penetration and endometrial changes that reduce the likelihood of implantation.
Acne is a skin condition with a multifactorial etiology, including androgen stimulation of sebum production. While the combination of ethinyl estradiol and norgestimate increases sex hormone-binding globulin (SHBG) and decreases free testosterone, the relationship between these changes and a decrease in the severity of facial acne in otherwise healthy women with this skin condition has not been established.
No specific pharmacodynamic studies were conducted with Sprintec.
Norgestimate (NGM) and EE are rapidly absorbed following oral administration. NGM is rapidly and completely metabolized by first pass (intestinal and/or hepatic) mechanisms to norelgestromin (NGMN) and norgestrel (NG), which are the major active metabolites of norgestimate.
Peak serum concentrations of NGMN and EE are generally reached by 2 hours after administration of Sprintec. Accumulation following multiple dosing of the 250 mcg NGM / 35 mcg EE dose is approximately 2-fold for NGMN and EE compared with single dose administration. The pharmacokinetics of NGMN is dose-proportional following NGM doses of 180 mcg to 250 mcg. Steady-state concentration of EE is achieved by Day 7 of each dosing cycle. Steady-state concentrations of NGMN and NG are achieved by Day 21. Non-linear accumulation (approximately 8 fold) of NG is observed as a result of high-affinity binding to SHBG, which limits its biological activity (Table 3).
Table 3: Summary of NGMN, NG and EE pharmacokinetic
|Mean (SD) Pharmacokinetic Parameters of Sprintec During a Three||Cyc le Study|
|Analyte||Cycle||Day||Cmax||tmax (h)||AUC0-24h||t:½ (h)|
|NGMN||1||1||1.78 (0.397)||1.19 (0.25)||9.9 (3.25)||18.4 (5.91)|
|3||21||2.19 (0.655)||1.43 (0.68)||18.1 (5.53)||24.9 (9.04)|
|NG||1||1||0.649 (0.49)||1.42 (0.69)||6.22 (2.46)||37.8 (14)|
|3||21||2.65 (1.11)||1.67 (1.32)||48.2 (20.5)||45 (20.4)|
|EE||1||1||92.2 (24.5)||1.2 (0.26)||629 (138)||10.1 (1.90)|
|3||21||147 (41.5)||1.13 (0.23)||1210 (294)||15 (2.36)|
|Cmax = peak serum concentration, tmax = time to reach
peak serum concentration, AUC0-24 = area under serum concentration vs time
curve from 0 to 24 hours, t½ = elimination half-life, NC = not calculated.
NGMN and NG: Cmax = ng/mL, AUC0-24 = h•ng/mL
EE: Cmax = pg/mL, AUC0-24 = h•pg/mL
The effect of food on the pharmacokinetics of Sprintec has not been studied.
NGMN and NG are highly bound ( > 97%) to serum proteins. NGMN is bound to albumin and not to SHBG, while NG is bound primarily to SHBG. EE is extensively bound ( > 97%) to serum albumin and induces an increase in the serum concentrations of SHBG.
NGM is extensively metabolized by first-pass mechanisms in the gastrointestinal tract and/or liver. NGM's primary active metabolite is NGMN. Subsequent hepatic metabolism of NGMN occurs and metabolites include NG, which is also active, and various hydroxylated and conjugated metabolites. Although NGMN and its metabolites inhibit a variety of P450 enzymes in human liver microsomes, under the recommended dosing regimen, the in vivo concentrations of NGMN and its metabolites, even at the peak serum levels, are relatively low compared to the inhibitory constant (K ). EE is also metabolized to various hydroxylated products and their glucuronide and sulfate conjugates.
The metabolites of NGMN and EE are eliminated by renal and fecal pathways. Following administration of 14C-norgestimate, 47% (45 to 49%) and 37% (16 to 49%) of the administered radioactivity was eliminated in the urine and feces, respectively. Unchanged NGM was not detected in the urine. In addition to 17-deacetyl norgestimate, a number of metabolites of NGM have been identified in human urine following administration of radiolabeled NGM. These include 18, 19-Dinor-17-pregn-4-en-20- yn-3-one,17-hydroxy-13-ethyl,(17α)-(-);18,19-Dinor-5&bata;17-pregnan-20-yn,3α,17&bata;-dihydroxy-13- ethyl,(17α), various hydroxylated metabolites and conjugates of these metabolites.
In three US clinical trials with norgestimate and ethinyl estradiol, 1,651 women aged 18 to 38 years were studied for up to 24 cycles, proving a total of 24,272 cycles of exposure. The racial demographic was about 73 to 86% Caucasian, 8 to 13% African-American, 6 to 14% Hispanic with the remainder Asian or Other ( ≤ 1%). There were no exclusions on the basis of weight; the weight range for women treated was 82 to 303 lbs, with a mean weight of about 135 lbs. The pregnancy rate was approximately 1 pregnancy per 100 women-years.
Last reviewed on RxList: 9/8/2016
This monograph has been modified to include the generic and brand name in many instances.
Additional Sprintec Information
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