Biotransformation of norgestimate in women

Alton, Kevin B.; Hetyei, Nancy; Shaw, Charles J.; Patrick, James E.

doi:10.1016/0010-7824(84)90055-6

Cited by 31 publications

(6 citation statements)

References 5 publications

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“…[17][18][19] Similarly, norgestimate is extensively metabolized to form metabolites such as 17-deacetyl norgestimate (primary, active circulating metabolite in the plasma), various hydroxylated metabolites, conjugates of these metabolites and others. 20 In contrast, tenofovir is eliminated as unchanged drug in the urine and is neither a substrate, inducer, nor inhibitor of CYP3A enzymes when evaluated in vitro or in a number of pharmacokinetic drug interaction studies in humans. 12 Moreover, to our knowledge, tenofovir DF has not been implicated in clinically relevant drugdrug interactions with a number of agents that are metabolized similarly to that of hormonal contraceptives.…”

Section: Discussionmentioning

confidence: 99%

Lack of Effect of Tenofovir Disoproxil Fumarate on Pharmacokinetics of Hormonal Contraceptives

Kearney

Mathias

2009

Pharmacotherapy

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Tenofovir DF and norgestimate-ethinyl estradiol are not involved in a clinically significant drug-drug interaction; tenofovir DF did not affect the steady-state pharmacokinetics of norgestimate or ethinyl estradiol, including the concentration at the end of the dosing interval. Both drugs were well tolerated when coadministered. Tenofovir DF is unlikely to affect the pharmacokinetics of hormonal oral contraceptives.

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Section: Discussionmentioning

confidence: 99%

Lack of Effect of Tenofovir Disoproxil Fumarate on Pharmacokinetics of Hormonal Contraceptives

Kearney

Mathias

2009

Pharmacotherapy

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“…Hepatic metabolism of NGMN occurs and metabolites include norgestrel, which is highly bound to sex-hormone binding globulin (SHBG), thereby limiting its biologic availability, and various hydroxylated and conjugated metabolites. [18][19][20] NGMN is bound to albumin and not to SHBG. 18 EE is also metabolized to various hydroxylated products and their glucuronide and sulfate conjugates.…”

Section: Metabolism Protein Binding and Eliminationmentioning

confidence: 95%

Transdermal Contraception

Creasy¹,

Abrams²,

Fisher³

2001

Semin Reprod Med

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This review summarizes the clinical studies involving the once-weekly Ortho Evra/Evra contraceptive patch. The patch delivers norelgestromin (NGMN), 150 microg, and ethinyl estradiol (EE), 20 microg, daily to the systemic circulation. The contraceptive patch provided ovulation suppression and cycle control similar to that of oral norgestimate 250 microg/EE 35 microg, significantly decreased mean maximum follicular diameter following a 3-day intentional delayed dosing phase when compared with oral levonorgestrel (LNG) 50/75/125 microg/EE 30/40/30 micorg and oral LNG 100 microg/EE 20 microg, and was as effective as oral LNG 50/75/125 microg/EE 30/40/30 microg and oral desogestrel 150 microg/EE 20 microg in altering cervical mucus composition (i.e., creating a scanty, viscous consistency). The contraceptive patch provided efficacy, cycle control, and safety comparable to that seen with oral LNG 50/75/125 microg/EE 30/40/30 microg, but women were able to correctly follow the weekly dosing regimen significantly more often than the daily oral contraceptive dosing regimen. Less than 2% of patches were replaced because of complete detachment in these trials. The patch was not associated with phototoxicity or photoallergy. The contraceptive patch, the only noninvasive, weekly birth control method that a woman can self-administer, will be a valuable addition to current contraceptive options.

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“…Since the patch is applied transdermally, first‐pass metabolism (via the gastrointestinal tract and/or liver) of NGMN and EE that would be expected with oral administration is avoided. Hepatic metabolism of NGMN, the primary active metabolite of norgestimate, occurs and metabolites include norgestrel, which is highly bound to sex‐hormone binding globulin (SHBG) thereby limiting its biologic availability, and various hydroxylated and conjugated metabolites [5, 19, 20]. EE is also metabolized to various hydroxylated products and their glucuronide and sulphate conjugates [21].…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of a contraceptive patch (Evra^™/Ortho Evra^™) containing norelgestromin and ethinyloestradiol at four application sites

Abrams¹,

Skee²,

Natarajan³

et al. 2002

Brit J Clinical Pharma

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Aims To determine the pharmacokinetic pro®le of norelgestromin (NGMN) and ethinyloestradiol (EE) following application of the contraceptive patch, Evra TM / Ortho Evra TM , at each of four anatomic sites (abdomen, buttock, arm, and torso). Methods Thirty-seven healthy, nonpregnant women aged 20±45 years participated in this open-label, four-period crossover study. Subjects were randomized to one of four treatment (site of application) sequences. Each patch was worn for 7 days, with a 1 month washout between treatments. Blood samples were collected before and at various times up to 240 h after application of each patch. Serum samples were assayed for NGMN and EE by validated methods. Results The serum concentration reference ranges for NGMN and EE are 0.6±1.2 ng ml x1 and 25±75 pg ml x1 , respectively, based on studies of the mean C ave of oral norgestimate 250 mg and EE 35 mg. For all application sites, mean concentrations of NGMN and EE remained within these ranges during the 7 day wear period. Absorption of NGMN and EE during patch application on the buttock, arm, and torso was equivalent. Absorption of NGMN and EE during patch application on the abdomen was approximately 20% less than observed for the other three sites, although mean serum concentrations were still within reference ranges. A previous study demonstrated therapeutic equivalence of patches worn on the abdomen vs other sites. Conclusions Serum concentrations of NGMN and EE from the contraceptive patch remain within the reference ranges throughout the 7 day wear period, regardless of the site of application (abdomen, buttock, arm, or torso).

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Biotransformation of norgestimate in women

Cited by 31 publications

References 5 publications

Lack of Effect of Tenofovir Disoproxil Fumarate on Pharmacokinetics of Hormonal Contraceptives

Lack of Effect of Tenofovir Disoproxil Fumarate on Pharmacokinetics of Hormonal Contraceptives

Transdermal Contraception

Pharmacokinetics of a contraceptive patch (Evra^™/Ortho Evra^™) containing norelgestromin and ethinyloestradiol at four application sites

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Biotransformation of norgestimate in women

Cited by 31 publications

References 5 publications

Lack of Effect of Tenofovir Disoproxil Fumarate on Pharmacokinetics of Hormonal Contraceptives

Lack of Effect of Tenofovir Disoproxil Fumarate on Pharmacokinetics of Hormonal Contraceptives

Transdermal Contraception

Pharmacokinetics of a contraceptive patch (Evra™/Ortho Evra™) containing norelgestromin and ethinyloestradiol at four application sites

Contact Info

Product

Resources

About

Pharmacokinetics of a contraceptive patch (Evra^™/Ortho Evra^™) containing norelgestromin and ethinyloestradiol at four application sites