It is generally considered that progestogens that are structurally related to norethisterone are pro-drugs and that their progestational activity is due to their conversion to norethisterone. After oral administration, norethisterone acetate and ethynodiol diacetate are rapidly converted to norethisterone by esterases during hepatic first-pass metabolism. Although less is known about the transformation of lynestrenol and norethynodrel, it appears that lynestrenol first undergoes hydroxylation at carbon 3 and then oxidation of the hydroxyl group to form norethisterone. Although there is no convincing evidence for the in-vivo transformation of norethynodrel to norethisterone, data from receptor binding tests and bioassays suggest that norethynodrel is also a pro-drug.
来源:Hazardous Substances Data Bank (HSDB)
代谢
norethynodrel的代谢产物以葡萄糖苷酸和硫酸盐的形式排出体外...
The /metabolic/ products /of norethynodrel/ are eliminated as glucuronides and sulfates...
...Metabolic studies of norethynodrel in women have revealed the presence of the two 3-hydroxy epimers. The recovery of the two...was not large due to extensive further metabolism by routes such as hydroxylation, but keto reduction appears as the major initial pathway.
Double-bond reduction is an important pathway for ... norethynodrel ... /gives/ rise to stereoisomers of 17alpha-ethynyl-5-estrane-3,17beta-diol as significant metabolites in women.
From less polar fractions, there were isolated 17alpha- ethynylestr-5(10)-ene-3alpha,17beta-diol, 17alpha-ethynylestr-5 (10)-ene-3beta,17beta-diol, 17 alpha-ethynyl-5beta-estrane-3alpha,17beta-diol, and 17alpha-ethynyl-5 alpha-estrane-3beta, 17 beta-diol.
◉ Summary of Use during Lactation:Norethynodrel is only available in the United States in combination oral contraceptive products. Based on the available evidence, expert opinion holds that nonhormonal methods are preferred during breastfeeding and progestin-only contraceptive are preferred over combined oral contraceptives in breastfeeding women, especially during the first 4 weeks postpartum. Those with an interest in a combination oral contraceptive should consult the record entitled, Contraceptives, Oral, Combined.
◉ Effects in Breastfed Infants:Abnormal breast enlargement was reported in a 3-week-old male breastfed infant whose mother was taking an oral contraceptive containing norethynodrel 25 mg and mestranol 100 mcg. The contraceptive was the probable cause of breast enlargement, but most likely the estrogen component mestranol rather than norethynodrel caused the effect.
◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date. However, progestins such as norethynodrel are not considered to suppress lactation.
A study analyzed data from a prospective cohort study of U.S. women from May 2005 through June 2007. Women were followed from the third trimester of pregnancy throughout the first year postpartum. Data from the subset of women who intended to breastfeed for 3 months or longer postpartum during their third trimester of pregnancy and who were using a contraceptive at 3 months postpartum were analyzed (n = 1349). Women who intended to breastfeed for at least 4 months and were taking a progestin-only oral contraceptive, such as norethynodrel, were 3.15 times more likely to be breastfeeding (exclusive or nonexclusive) at 4 months than women who used a nonhormonal contraceptive. Women who said they would breastfeed for 3 to 4 months had 4-month breastfeeding rates equivalent to those using a nonhormonal contraceptive. These rates were much higher than those of women who were taking an estrogen-containing, combined oral contraceptive.
/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/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
解毒与急救
/SRP:/ 高级治疗：对于无意识、严重肺水肿或严重呼吸困难的病人，考虑进行口咽或鼻咽气管插管以控制气道。使用气囊面罩装置的正压通气技术可能有益。考虑使用药物治疗肺水肿……。对于严重的支气管痉挛，考虑给予β激动剂，如沙丁胺醇……。监测心率和必要时治疗心律失常……。开始静脉输注D5W /SRP: "保持开放"，最低流量/。如果出现低血容量的迹象，使用0.9%生理盐水（NS）或乳酸林格氏液。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象……。使用地西泮或劳拉西泮治疗癫痫……。使用丙美卡因氢氯化物协助眼部冲洗……。 /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/
/CASE REPORTS/ A 48-yr-old woman with chronic intestinal ischemia and a long history of oral contraceptive use is reported. She presented with a 6-month history of severe diarrhea, abdominal pain, and weight loss. Abdominal arteriography revealed occlusion of the celiac axis at its origin and 90% stenosis of the superior mesenteric artery. This chronic arterial lesion has not been previously noted in association with the use of oral contraceptive agents in otherwise healthy women. The patient's isolated arterial lesions proved amenable to successful surgical bypass. Postoperatively she became completely asymptomatic and has remained so on long-term follow-up.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
在女性中代谢；急性口服剂量的75%在7天内通过尿液和粪便排出，尿液中有复杂的代谢物模式。
...Metabolized in women; 75% of an acute oral dose was excreted in 7-day urine and feces, with complex pattern of urinary metabolites.
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.
Deuterated analogs of (4S)-4-Ethyl-4-hydroxy-11-[2- (trimethylsilyl)ethyl]-1H-pyrano[3', 4':6,7] indolizino [1,2-b]quinoline-3,14(4H, 12H)-dione and methods of use thereof
申请人：Chen Xinghai
公开号：US20120282261A1
公开（公告）日：2012-11-08
The present invention discloses: (i) two novel deuterated Karenitecin® analogs, pharmaceutically-acceptable salts, and/or derivatives thereof; (ii) methods of synthesis of said novel deuterated Karenitecin® analogs, pharmaceutically-acceptable salts, and/or derivatives thereof; (iii) pharmaceutically-acceptable formulations comprising said novel deuterated Karenitecin® analogs, pharmaceutically-acceptable salts, derivatives thereof; and/or, optionally, one or more additional chemotherapeutic agents; and (iv) methods of administration of said novel deuterated Karenitecin® analogs, pharmaceutically-acceptable salts, derivatives thereof; and/or, optionally, one or more additional chemotherapeutic agents, to subjects in need thereof.
[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.
[EN] BIOREVERSABLE PROMOIETIES FOR NITROGEN-CONTAINING AND HYDROXYL-CONTAINING DRUGS<br/>[FR] PRO-FRAGMENTS BIORÉVERSIBLES POUR MÉDICAMENTS CONTENANT DE L'AZOTE ET DE L'HYDROXYLE
申请人：BAIKANG SUZHOU CO LTD
公开号：WO2015081891A1
公开（公告）日：2015-06-11
Disclosed are promoieties of the following formula which can be used to form prodrugs of nitrogen-containing or hydroxyl-containing drug or a pharmaceutically active agent: (I) and pharmaceutical compositions comprising the prodrugs.
