Actions of Norethisterone in details
Pharmacology: Pharmacodynamics: Norethisterone administration increases the protein and sialic acid content of cervical mucus which prevents penetration of the mucus by spermatozoa. It causes changes in the structure of the endometrium such that implantation of blastocysts is impaired. It also reduces numbers and height of cilia on cells lining the fallopian tube, which could delay tubal transport of ova.
Pharmacokinetics: Norethisterone is rapidly and completely absorbed after oral administration, peak plasma concentrations occurring in the majority of subjects between 1 and 3 hours. Due to first-pass metabolism, blood levels after oral administration are 60% of those after i.v. administration. The half-life of elimination varies from 5 to 12 hours, with a mean of 7.6 hours.
Norethisterone is metabolised mainly in the liver. Approximately 60% of the administered dose is excreted as metabolites in urine and faeces.
Toxicology: Preclinical Safety Data: The toxicity of Norethisterone is very low. Reports of teratogenic effects in animals are uncommon. No carcinogenic effects have been found even in long-term studies. In subacute and chronic studies only minimal differences between treated and control animals are observed.
Norethisterone administration
May be taken with or without food.
Norethisterone pharmacology
Norethisterone Acetate induces secretory changes in an estrogen-primed endometrium. On a weight basis, it is twice as potent as Norethisterone.
Pharmacokinetics
Absorption
Norethisterone Acetate is completely and rapidly deacetylated to Norethisterone (NET) after oral administration, and the disposition of Norethisterone Acetate is indistinguishable from that of orally administered Norethisterone. Norethisterone Acetate is rapidly absorbed from Norethisterone Acetate tablets, with maximum plasma concentration of Norethisterone generally occurring at about 2 hours post-dose. The pharmacokinetic parameters of Norethisterone following single oral administration of Norethisterone Acetate in 29 healthy female volunteers are summarized in Table 1.
| Norethisterone Acetate (n=29) | Arithmetic Mean ± SD |
|---|---|
| AUC = area under the curve, Cmax = maximum plasma concentration, tmax = time at maximum plasma concentration, t1/2 = half-life, SD = standard deviation. | |
| Norethisterone (NET) | |
| AUC (0-inf)(ng/mL*h) | 166.9 ± 56.28 |
| Cmax (ng/mL) | 26.19 ± 6.19 |
| tmax (h) | 1.83 ± 0.58 |
| t1/2 (h) | 8.51 ± 2.19 |
Effect of Food
The effect of food administration on the pharmacokinetics of Norethisterone Acetate has not been studied.
Distribution
Norethisterone is 36% bound to sex hormone-binding globulin (SHBG) and 61% bound to albumin. Volume of distribution of Norethisterone is about 4 L/kg.
Metabolism
Norethisterone undergoes extensive biotransformation, primarily via reduction, followed by sulfate and glucuronide conjugation. The majority of metabolites in the circulation are sulfates, with glucuronides accounting for most of the urinary metabolites.
Excretion
Plasma clearance value for Norethisterone is approximately 0.4 L/hr/kg. Norethisterone is excreted in both urine and feces, primarily as metabolites. The mean terminal elimination half-life of Norethisterone following a single dose administration of Norethisterone Acetate is approximately 9 hours.
Special Populations
Geriatrics
The effect of age on the pharmacokinetics of Norethisterone after Norethisterone Acetate administration has not been evaluated.
Race
The effect of race on the disposition of Norethisterone after Norethisterone Acetate administration has not been evaluated.
Renal Insufficiency
The effect of renal disease on the disposition of Norethisterone after Norethisterone Acetate administration has not been evaluated. In premenopausal women with chronic renal failure undergoing peritoneal dialysis who received multiple doses of an oral contraceptive containing ethinyl estradiol and Norethisterone, plasma Norethisterone concentration was unchanged compared to concentrations in premenopausal women with normal renal function.
Hepatic Insufficiency
The effect of hepatic disease on the disposition of Norethisterone after Norethisterone Acetate administration has not been evaluated. However, Norethisterone Acetate is contraindicated in markedly impaired liver function or liver disease.
Drug Interactions
No pharmacokinetic drug interaction studies investigating any drug-drug interactions with Norethisterone Acetate have been conducted.
References
- DailyMed. "NORETHINDRONE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
- NCIt. "Norethindrone: NCI Thesaurus (NCIt) provides reference terminology for many systems. It covers vocabulary for clinical care, translational and basic research, and public information and administrative activities.". https://ncit.nci.nih.gov/ncitbrowser... (accessed September 17, 2018).
- EPA DSStox. "Norethindrone: DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology.". https://comptox.epa.gov/dashboard/ds... (accessed September 17, 2018).
Reviews
The results of a survey conducted on ndrugs.com for Norethisterone are given in detail below. The results of the survey conducted are based on the impressions and views of the website users and consumers taking Norethisterone. We implore you to kindly base your medical condition or therapeutic choices on the result or test conducted by a physician or licensed medical practitioners.User reports
3 consumers reported administration
When best can I take Norethisterone, on an empty stomach, before or after food?ndrugs.com website users have also released a report stating that Norethisterone should be taken After food. In any case, this may not be the right description on how you ought to take this Norethisterone. Kindly visit your doctor for more medical advice in this regard. Click here to see other users view on when best the Norethisterone can be taken.
| Users | % | ||
|---|---|---|---|
| After food | 2 | 66.7% | |
| Empty stomach | 1 | 33.3% | |
Consumer reviews
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Information checked by Dr. Sachin Kumar, MD Pharmacology
