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/
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] PURE D-(17alpha)-13-ETHYL-17-HYDROXY-18,19-DINORPREGN-4-ENE-20-YNE-3-ONE-3E- AND -3Z-OXIME ISOMERS, AS WELL AS PROCESS FOR THE SYNTHESIS OF THE MIXTURE OF ISOMERS AND THE PURE ISOMERS [FR] ISOMERES PURS DE D-(17 DOLLAR G(A))-13-ETHYL-17-HYDROXY-18,19-DINORPREGN-4-EN-20-YN-3-ONE-3E- ET -3Z-OXIME, ET PROCEDE POUR REALISER LA SYNTHESE DU MELANGE D'ISOMERES ET D'ISOMERES PURS
6,7-Dihydro-5H-benzo[7]annulene derivatives, processes for their preparation, pharmaceutical products comprising them and their use for preparing medicaments
申请人：Bayer Intellectual Property GmbH
公开号：US20150080438A1
公开（公告）日：2015-03-19
The invention relates to selective oestrogen receptor modulators (SERMs) and to processes for their preparation, to their use for the treatment and/or prophylaxis of diseases and to their use for preparing medicaments for the treatment and/or prophylaxis of diseases, in particular of bleeding disorders, osteoporosis, endometriosis, myomata, hormone-dependent tumours, for hormone replacement therapy and for contraception.
Process for the synthesis of high purity D-(17a)-13-ethyl-17-hydroxy-18,19-dinorpregn-4-ene-20-yn-3-one oxime
申请人：Tuba Zoltan
公开号：US20050032763A1
公开（公告）日：2005-02-10
The invention relates to a process for the synthesis of d-(17α)-13-ethyl-17-hydroxy-18,19-dinorpregn-4-ene-20-yn-3-one-oxime (also known as norelgestromin) via acetylation of d-norgestrel at position 17; oximation of the oxo group at position 3 of the obtained d-(17α)-13-ethyl-17-(acetyloxy)-18,19-dinorpregn-4-ene-20-yn-3-one; and then hydrolyzing the acetyloxy group at position 17 of the obtained d-(17α)-13-ethyl-17-(acetyloxy)-18,19-dinorpregn-4-ene-20-yn-3-oxime derivative, thereby obtaining norelgestromin.
Formulations and methods for vaginal delivery of antiprogestins
申请人：REPROS THERAPEUTICS INC.
公开号：US10064815B2
公开（公告）日：2018-09-04
The subject matter of the present invention is pertinent to the field of vaginal delivery of pharmaceutically active agents. Embodiments of the instant invention disclose methods for treating a variety of progesterone related disorders by vaginal administration of a pullulan capsule and a fill formulation comprising one or more antiprogestins dispersed in a mixture of isopropyl palmitate or isopropyl myristate and a polyethylene glycol.
Pharmaceutical composition comprising progestogens and/or estrogens and 5-methyl-(6S)-tetrahydrofolate
申请人：MERCK & CIE
公开号：US10463666B2
公开（公告）日：2019-11-05
The present invention relates to a pharmaceutical composition which comprises progestogens, preferably drospirenone, estrogens, preferably ethinylestradiol and 5-methyl-(6S)-tetrahydrofolate, can be employed as oral contraceptive and moreover prevents disorders caused by folate deficiency in the consumers, in particular cardiovascular disorders and, after conception of the embryo, congenital malformations caused by folate deficiency such as, for example, neural tube defects, ventricular valve defects, urogenital defects, and cleft lip, jaw and palate, without masking the symptoms of vitamin B12 deficiency, and at the same time even in the case of homozygous or heterozygous polymorphism of methylenetetrahydrofolate reductase facilitates unimpaired utilizability of the folate component 5-methyl-(6S)-tetrahydrofolate by the body and thus its biological activity for preventing the abovementioned congenital malformations caused by folate deficiency. In addition, a prolonged protective effect is maintained after discontinuation of the contraceptive.
Formulations and methods for vaginal delivery of antiprogenstins
申请人：Repros Therapeutics Inc.
公开号：US10555900B2
公开（公告）日：2020-02-11
The subject matter of the present invention is pertinent to the field of vaginal delivery of pharmaceutically active agents. Embodiments of the instant invention disclose methods for treating a variety of progesterone related disorders by vaginal administration of a pullulan capsule and a fill formulation comprising one or more antiprogestins dispersed in a mixture of isopropyl palmitate or isopropyl myristate and a polyethylene glycol.
