Norgestimate 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.
Norgestimate is extensively metabolized by first-pass mechanisms in the gastrointestinal tract and/or liver. Norgestimate's primary active metabolite is norelgestromin. Subsequent hepatic metabolism of norelgestromin occurs and metabolites include norgestrel, which is also active, and various hydroxylated and conjugated metabolites.
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,(17alpha)-(-); 18,19-Dinor-5beta-17-pregnan-20-yn,3alpha,17beta-dihydroxy-13-ethyl,(17alpha), various hydroxylated metabolites and conjugates of these metabolites.
There is limited information on the metabolism of levonorgestrel, norethindrone and structurally related contraceptive steroids. Both levonorgestrel and norethindrone undergo extensive reduction of the alpha, beta-unsaturated ketone in ring A. Levonorgestrel also undergoes hydroxylation at carbons 2 and 16. The metabolites of both compounds circulate predominantly as sulfates. In urine, levonorgestrel metabolites are found primarily in the glucuronide form, whereas norethindrone metabolites are present in approximately equal amounts as sulfates and glucuronides. Of the progestogens structurally related to norethindrone, norethindrone acetate, ethynodiol diacetate, norethindrone enanthate, and perhaps lynestrenol, undergo rapid hydrolysis and are converted to the parent compound and its metabolites. There is no convincing evidence that norethynodrel is converted to norethindrone. Of the progestogens structurally related to levonorgestrel, it appears that neither desogestrel nor gestodene are transformed to the parent compound. However, there is evidence that norgestimate can be, at least partly, converted to levonorgestrel. ...
Herbal products containing St. John's Wort (hypericum perforatum) may induce hepatic enzymes (cytochrome P450) and p-glycoprotein transporter and may reduce the effectiveness of contraceptive steroids. This may also result in breakthrough bleeding.
Combined hormonal contraceptives have been shown to significantly decrease plasma concentrations of lamotrigine when co-administered due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary.
/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/
/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/
/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
诺孕酯（NGM）和炔雌醇（EE）在口服给药后迅速吸收。
Norgestimate (NGM) and ethinyl estradiol (EE) are rapidly absorbed following oral administration.
Peak serum concentrations of norelgestromin (NGMN) and ethinyl estradiol (EE) are generally reached by 2 hours after administration of MonoNessa. Accumulation following multiple dosing of the 250 ug Norgestimate (NGM)/ 35 ug 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 ug to 250 ug. ... Steady-state concentrations of NGMN and NG are achieved by Day 21. Non-linear accumulation (approximately 8 fold) of norgestrel is observed as a result of high affinity binding to SHBG (sex hormone-binding globulin), which limits its biological activity.
Norelgestromin and norgestrel are highly bound (>97%) to serum proteins. Norelgestromin is bound to albumin and not to SHBG, while norgestrel is bound primarily to SHBG.
The metabolites of norelgestromin and ethinyl estradiol are 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.
[EN] PROCESS FOR THE SYNTHESIS OF HIGH PURITY D-(17ALPHA)-13-ETHYL-17HYDROXY-18,19-DINORPRE:GN-4-ENE-20-YNE-3-ONE-OXIME [FR] PROCEDE DE SYNTHESE D'UNE D-(17ALPHA)-13-ETHYL-17-HYDROXY-18,19-DINOR-PREGN-4-ENE-20-YNE-3-ONE-OXIME TRES PURE
Dibenzyl amine compounds and derivatives, pharmaceutical compositions containing such compounds and the use of such compounds to elevate certain plasma lipid levels, including high density lipoprotein-cholesterol and to lower certain other plasma lipid levels, such as LDL-cholesterol and triglycerides and accordingly to treat diseases which are exacerbated by low levels of HDL cholesterol and/or high levels of LDL-cholesterol and triglycerides, such as atherosclerosis and cardiovascular diseases in some mammals, including humans.
SELF-ASSEMBLY OF THERAPEUTIC AGENT-PEPTIDE NANOSTRUCTURES
申请人：Ohio State Innovation Foundation
公开号：US20140155577A1
公开（公告）日：2014-06-05
Disclosed are conjugates of hydrophobic drugs linked to protected or unprotected amino acids or peptides. The disclosed conjugates are amphiphilic and can self assemble into nanotubes. Nanotubes comprising the conjugates are also described and can have high loading of the drug and protect it from degradation or elimination. The nanotubes are well suited to deliver hydrophobic and unstable drugs to individuals.
Pyrrolidine and related derivatives useful as PR modulators
申请人：Commons Thomas Joseph
公开号：US20080045560A1
公开（公告）日：2008-02-21
Compounds of the following structure are described:
wherein R
1
-R
6
, R
11
, R
12
, m, V, X, Y, Z and Q are described herein, or a pharmaceutically acceptable salt, tautomer, metabolite or prodrug thereof. These compounds are useful for treating a variety of hormone-related conditions including contraception, treating or preventing fibroids, endometriosis, dysfunctional bleeding, uterine leiomyomata, polycystic ovary syndrome, or hormone-dependent carcinomas, providing hormone replacement therapy, stimulating food intake or synchronizing estrus.
Tricyclic oxazolidone derivatives useful as PR modulators
申请人：Commons Thomas Joseph
公开号：US20080045578A1
公开（公告）日：2008-02-21
Compounds of the following structure are described:
wherein R
1
-R
6
, R
16
, m, V, W, X, Y, and Q are described herein, or a pharmaceutically acceptable salt, tautomer, metabolite or prodrug thereof. These compounds are useful for treating a variety of hormone-related conditions including contraception, treating or preventing fibroids, endometriosis, dysfunctional bleeding, uterine leiomyomata, polycystic ovary syndrome, or hormone-dependent carcinomas, providing hormone replacement therapy, stimulating food intake or synchronizing estrus.
[EN] HETEROCYCLIC COMPOUNDS AND THEIR USE AS RETINOID-RELATED ORPHAN RECEPTOR (ROR) GAMMA-T INHIBITORS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES ET LEUR UTILISATION EN TANT QU'INHIBITEURS GAMMA-T DU RÉCEPTEUR ORPHELIN APPARENTÉ AUX RÉCEPTEURS DES RÉTINOÏDES (ROR) )
申请人：TAKEDA PHARMACEUTICAL
公开号：WO2016002968A1
公开（公告）日：2016-01-07
Provided are heterocyclic compounds having a RORγt inhibitory action represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof.
