Desogestrel is rapidly metabolized in the intestinal mucosa and by first-pass hepatic metabolism to form the major metabolite of desogestrel is [etonogestrel] which is the biologically active metabolite. This modification is described by the hydroxylation in C3 of the desogestrel molecule. Later, etonogestrel is metabolized following the normal pathways of steroid metabolism. On the other hand, due to the 11-methylene side chain, desogestrel cannot be metabolized to other progestins.
In addition to 3-keto-desogestrel, other phase I metabolites are 3alpha-OH-desogestrel, 3beta-OH-desogestrel, and 3alpha-OH-5alpha-H-desogestrel. These other metabolites are not known to have any pharmacologic effects, and are further converted in part by conjugation (phase II metabolism) into polar metabolites, mainly sulfates and glucuronides.
Desogestrel is metabolized via hydroxylation and dehydrogenation to the active metabolite etonogestrel. Etonogestrel is metabolised via sulphate and glucuronide conjugation.
来源:Hazardous Substances Data Bank (HSDB)
代谢
屈螺酮是一种高效的孕激素，通过抑制垂体促性腺激素的分泌，从而抑制卵巢排卵。
Desogestrel is metabolized rapidly and completely in the liver and gut wall. It is metabolized to 3-keto-desogestrel, which mediates its progestogenic effects, and it is not metabolized further to another progestogen. The serum concentrations of 3-keto-desogestrel reached maximum levels within 2-3 hours after oral administration of desogestrel and were subsequently cleared with a half-life of 12-24 hours.
The metabolism of desogestrel in microsomes from six hours livers in vitro /were studied/. The main metabolite formed was 3-keto-desogestrel; 3alpha-hydroxydesogestrel and 3beta-hydroxydesogestrel were also detected. The metabolism of desogestrel was inhibited by 50% by primaquine at a concentration of 30 umol/L, but not by levonorgestrel at 250 umol/L.
◉ Summary of Use during Lactation:Desogestrel is only available in the United States in combination oral contraceptive products containing 150 mcg of desogestrel and 30 mcg of ethinyl estradiol. 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. For further information, consult the record entitled, Contraceptives, Oral, Combined.
◉ Effects in Breastfed Infants:A nonblinded, nonrandomized study compared oral desogestrel 75 mcg alone daily (n = 42) to an intrauterine device (IUD; n = 40) begun 28 to 56 days postpartum for contraception. No differences in infant length, weight or biparietal head circumferences were found after 1, 4, and 7 treatment cycles. Temporary breast enlargement was reported in 2 infants and increased sweating was reported in 1 infant in the desogestrel group, compared with no adverse effects reported in infants in the IUD group. The growth of some infants were again measured at 1.5 and 2.5 years; no clinically important differences were found.
A breastfed (extent not stated) infant developed scrotal hair at 4 months of age. His mother had received the progestin, dydrogestrone, during the first trimester of pregnancy and began taking desogestrel 0.075 mg daily as a contraceptive beginning at 3 months postpartum. His mother discontinued desogestrel after 28 days and the scrotal hair resolved by 11 months of age. Desogestrel was a possible contributing cause of scrotal hair growth in this infant.
◉ Effects on Lactation and Breastmilk:A nonblinded, nonrandomized study compared oral desogestrel 75 mcg alone daily (n = 42) to an intrauterine device (n = 40) begun 28 to 56 days postpartum for contraception. During the 7-month trial period, 1 woman dropped out of the trial because of diminished lactation compared with none in the IUD group. At the end of the first and fourth treatment cycle, there were no differences in the amount of milk produced between the desogestrel and IUD groups. No differences in triglyceride, protein or lactose content of milk were found at the end of 1, 4, and 7 cycles of therapy.
A nonrandomized study followed 200 women given a desogestrel-only contraceptive 75 mcg daily for 6 months beginning at 6 weeks postpartum and compared them to 200 women who received placebos. No difference was found in the amounts of milk production or infant growth and development between the two groups.
In a nonblinded, nonrandomized study in Turkey of 4964 postpartum women were given the option of desogestrel 75 mcg (Cerazette) as a contraceptive starting at 21 days postpartum. On follow-up, the percentages of women who were breastfeeding at the third, sixth and ninth months postpartum were 68.4%, 54.8% and 58.5%, respectively. The authors concluded that the contraceptive had no negative impact on breastfeeding.
/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"，最小流量/。如果出现低血容量的迹象，使用0.9%的生理盐水（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/
/HUMAN EXPOSURE STUDIES/ This study investigated the effect of transdermal T and oral desogestrel on the reproductive axis of healthy men. Twenty-three men were randomized to 1 of 3 treatment groups and received a daily transdermal T patch plus oral desogestrel at a dose of 75, 150, or 300 ug/d for 24 weeks. Baseline blood and semen samples were obtained and then every 4 weeks thereafter for 32 weeks. The outcome measures were sperm density and plasma levels of FSH, LH, total and free T. The results show a dose-dependent suppression of spermatogenesis and gonadotropins. Seven of the 17 subjects became azoospermic. Desogestrel (300 ug daily) in combination with 5 mg daily transdermal T was the most effective (57% azoospermic), whereas a dose of 75 ug was ineffective (0% azoospermic). Total and free plasma T were reduced by approximately 30%. High density lipoprotein cholesterol was significantly reduced. No serious side-effects were encountered. ...
After oral administration, desogestrel is rapidly absorbed and it reaches a peak concentration of 2 ng/ml after 1.5 hours. The bioavailability of desogestrel is reported to be in the range of 60-80% and the reported AUC is of 3000 ng.h/ml. Almost all the administered dose is modified to the active metabolite, [etonogestrel].
The elimination of desogestrel is found to be mainly renal corresponding to about 6 times the dose eliminated in the bile. The elimination of desogestrel is only done as the metabolites and not as the unchanged drug and about 85% of the administered dose can be excreted as metabolites after 6-8 days.
来源:DrugBank
吸收、分配和排泄
分布容积
去氧孕烯的表观分布容积为1.5 L/kg。
The apparent volume of distribution of desogestrel is of 1.5 L/kg.
来源:DrugBank
吸收、分配和排泄
清除
去氧孕烯的代谢清除率据报道约为2毫升/分钟/千克。
The metabolic clearance rate of desogestrel is reported to be of about 2 ml/min/kg.
After oral dosing of Cerazette desogestrel (DSG) is rapidly absorbed and converted into etonogestrel (ENG). Under steady-state conditions, peak serum levels are reached 1.8 hours after tablet-intake and the absolute bioavailability of ENG is approximately 70%.
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.
