_In vitro_, oxymetazoline was minimally metabolized by human liver enzymes to produce mono-oxygenated and dehydrogenated metabolites. About 95.9% of the total dose of oxymetazoline remained as an unchanged parent compound after a 120-minute incubation with human liver microsomes. When incubated in rat, rabbit, and human liver post-mitochondrial supernatant fraction from homogenized tissue (S9) fractions, oxymetazoline was more efficiently metabolized by rabbit liver S9 fractions (~65%) than by rat (~20%) or human (~10%) liver S9 fractions. At concentrations (50 μM) at least 130-fold greater than the usual therapeutic intranasal dose (400 nM), CYP2C19 was suggested to be involved in the oxidation of oxymetazoline following intranasal administration; however, metabolites in humans have not been fully characterized up to date and remain speculated based on _in vitro_ studies using rat and rabbit liver S9 fractions and microsomes. The O-glucuronide metabolite catalyzed by UGT1A9 has been identified _in vitro_.
◉ Summary of Use during Lactation:Although no information exists on the use of oxymetazoline specifically during breastfeeding, very little should reach the infant through breastmilk because of the local administration and limited absorption into the maternal bloodstream. It is recommended over oral systemic decongestants such as pseudoephedrine during breastfeeding. Topical use on the face is unlikely to present a risk to the nursing infant.
◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.
◈ What is oxymetazoline?
Oxymetazoline is a medication in nasal sprays (sprayed into nostrils) and topical preparations (applied to skin). Oxymetazoline is used treat nasal congestion, eye inflammation, and skin redness. It works by constricting blood vessels (making the blood vessels smaller). Oxymetazoline can be found in prescription products and in many over the counter products. Some examples are: Afrin®, Dristan®, Nostrilla®, Rhofade®, and Vicks®.Sometimes when people find out they are pregnant, they think about changing how they take their medication, or stopping their medication altogether. However, it is important to talk with your healthcare providers before making any changes to how you take this medication. Your healthcare providers can talk with you about the benefits of treating your condition and the risks of untreated illness during pregnancy.
◈ I take oxymetazoline. Can it make it harder for me to get pregnant?
It is not known if oxymetazoline can make it harder to get pregnant.
◈ Does taking oxymetazoline increase the chance for miscarriage?
Miscarriage can occur in any pregnancy. Studies have not been done to see if oxymetazoline increases the chance for miscarriage.
◈ Does taking oxymetazoline increase the chance of birth defects?
Every pregnancy starts out with a 3-5% chance of having a birth defect. This is called the background risk. Based on the studies reviewed, oxymetazoline is not expected to increase the chance for birth defects above the background risk.
◈ Does taking oxymetazoline in pregnancy increase the chance of other pregnancy-related problems?
A report of 12 pregnancies in healthy people exposed to a one-time nasal spray dose of oxymetazoline showed no effect on uterine blood flow. Studies have not been done to see if oxymetazoline increases the chance for pregnancy-related problems such as preterm delivery (birth before week 37) or low birth weight (weighing less than 5 pounds, 8 ounces [2500 grams] at birth).
◈ Does taking oxymetazoline in pregnancy affect future behavior or learning for the child?
Studies have not been done to see if oxymetazoline can cause behavior or learning issues for the child.Breastfeeding while taking oxymetazoline:Oxymetazoline has not been well-studied for use while breastfeeding. Since oxymetazoline is sprayed into nose or rubbed onto skin, it is thought that very little of the medication could reach breastmilk. Be sure to talk to your healthcare provider about all of your breastfeeding questions.
◈ If a male takes oxymetazoline, could it affect fertility (ability to get partner pregnant) or increase the chance of birth defects?
Studies have not been done to see if oxymetazoline could affect male fertility or increase the chance of birth defects. In general, exposures that fathers or sperm donors have are unlikely to increase the risks to a pregnancy. For more information, please see the MotherToBaby fact sheet Paternal Exposures at https://mothertobaby.org/fact-sheets/paternal-exposures-pregnancy/.
If significant systemic absorption of nasal /or ophthalmic/ oxymetazoline occurs, concurrent use of maprotiline or tricyclic antidepressants may potentiate the pressor effect of oxymetazoline.
A case is described in which a 34 yr old man presented with severe hypertension, cardiomegaly, and congestive heart failure, presumably due to oxymetazoline hydrochloride, phenylephrine hydrochloride, and ephedrine hydrochloride, consumed in massive doses by an overuse of nasal decongestants and cough syrup. Coadamin chlorpromazine hydrochloride and trimeprazine tartrate may have contributed to the effects through anticholinergic and antihistamine properties. The patient was treated with furosemide and nifedipine. Signs and symptoms of heart failure quickly resolved and blood pressure dropped to 140/100 mm Hg. /Oxymetazoline hydrochloride/
Self-treatment of anaphylaxis due to a single 75 mg dose of ketoprofen is reported in a 39 yr old female patient who used 12 inhalations of an oxymetazoline nasal solution in each nostril to relieve the respiratory symptoms of the allergic reaction. Within min of using the nasal solution, the respiratory symptoms began to subside, and the patient slept through the night and consulted her doctor the next day.
Imidazole derivatives such as oxymetazoline are readily absorbed across mucosal membranes, especially in children. In adult subjects with erythema associated with rosacea, the mean ± standard deviation (SD) Cmax was 60.5 ± 53.9 pg/mL and the AUC from time 0 to 24 hours (AUC0-24hr) was 895 ±798 pg x hr/mL following topical administration of first-dose oxymetazoline. Following once-daily topical applications for 28 days, the mean ± SD Cmax was 66.4 ± 67.1 pg/mL and the AUC0-24hr was 1050 ± 992 pg x hr/mL. Following twice-daily applications for 28 days, the mean ± SD Cmax was 68.8 ± 61.1 pg/mL and the AUC0-24hr was 1530 ± 922 pg x hr/mL. Following single-drop ocular administration of oxymetazoline in healthy adult subjects, the mean ± SD Cmax was 30.5 ± 12.7 pg/mL and the area under the concentration-time curve (AUCinf) was 468 ± 214 pg x hr/mL. The median Tmax was 2 hours, ranging from 0.5 to 12 hours. Following nasal administration of an 0.6 mL combination product containing tetracaine and oxymetazoline in adult subjects, the maximum concentrations of oxymetazoline were reached within approximately 10 minutes. The mean Cmax was 1.78 ng/mL and the AUC0-inf value was 4.24 ng x h/mL, with a median Tmax of 5 minutes.
While the excretion of oxymetazoline following nasal, topical, or ophthalmic administration of oxymetazoline has not been fully characterized in humans, it is believed that the predominant route of elimination at clinically relevant concentrations of oxymetazoline is renal excretion.
来源:DrugBank
吸收、分配和排泄
分布容积
关于羟甲唑啉的分布体积的信息有限。
There is limited information on the volume of distribution of oxymetazoline.
来源:DrugBank
吸收、分配和排泄
清除
有关氧甲唑啉的清除率信息有限。
There is limited information on the clearance rate of oxymetazoline.
... Oxymetazoline /at an optimum strength of 0.025%/ was absorbed slowly into the eye: only 0.006% of the original drug concentration was found in the aqueous humors of rabbits 30 minutes after instillation; the balance remained primarily in external ocular tissues. Metabolic studies in rabbits indicated that excreted amounts of unmetabolized radioactive oxymetazoline in urine following drug administration were similar (23%) for the ocular and nasal routes of application. The proportions of oxymetazoline metabolite to unchanged oxymetazoline were constant for all administration routes tested.
[EN] COMPOSITION AND METHODS FOR THE TREATMENT OF ANAL AND RECTAL DISORDERS [FR] COMPOSITION ET PROCÉDÉS POUR LE TRAITEMENT DE TROUBLES ANAUX ET RECTAUX
[EN] COMPOSITION AND METHODS FOR THE TREATMENT OF ANAL AND RECTAL DISORDERS [FR] COMPOSITION ET PROCÉDÉS POUR LE TRAITEMENT DE TROUBLES ANAUX ET RECTAUX
[EN] NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS<br/>[FR] NOUVEAUX COMPOSÉS ET COMPOSITIONS PHARMACEUTIQUES LES COMPRENANT POUR LE TRAITEMENT DE TROUBLES INFLAMMATOIRES
申请人：GALAPAGOS NV
公开号：WO2017012647A1
公开（公告）日：2017-01-26
The present invention discloses compounds according to Formula (I), wherein R1, R3, R4, R5, L1, and Cy are as defined herein. The present invention also provides compounds, methods for the production of said compounds of the invention, pharmaceutical compositions comprising the same and their use in allergic or inflammatory conditions, autoimmune diseases, proliferative diseases, transplantation rejection, diseases involving impairment of cartilage turnover, congenital cartilage malformations, and/or diseases associated with hypersecretion of IL6 and/or interferons. The present invention also methods for the prevention and/or treatment of the aforementioned diseases by administering a compound of the invention.
[EN] METHYL OXAZOLE OREXIN RECEPTOR ANTAGONISTS<br/>[FR] MÉTHYLOXAZOLES ANTAGONISTES DU RÉCEPTEUR DE L'OREXINE
申请人：MERCK SHARP & DOHME
公开号：WO2016089721A1
公开（公告）日：2016-06-09
The present invention is directed to methyl oxazole compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which orexin receptors are involved.
3-Aminocyclopentanecarboxamides as modulators of chemokine receptors
申请人：Xue Chu-Biao
公开号：US20060004018A1
公开（公告）日：2006-01-05
The present invention is directed to compounds of Formula I:
which are modulators of chemokine receptors. The compounds of the invention, and compositions thereof, are useful in the treatment of diseases related to chemokine receptor expression and/or activity.
[EN] COMPOUNDS THAT MODULATE EGFR ACTIVITY AND METHODS FOR TREATING OR PREVENTING CONDITIONS THEREWITH<br/>[FR] COMPOSÉS MODULANT L'ACTIVITÉ DES RÉCEPTEURS EGFR ET MÉTHODES POUR TRAITER OU PRÉVENIR DES TROUBLES À L'AIDE DE CEUX-CI
申请人：GATEKEEPER PHARMACEUTICALS INC
公开号：WO2011140338A1
公开（公告）日：2011-11-10
Provided are compounds and methods for treating or preventing kinase-mediated disorders therewith.
提供了用于治疗或预防激酶介导的疾病的化合物和方法。
Benzoxazinyl-amidocyclopentyl-heterocyclic modulators of chemokine receptors
申请人：Goble D. Stephen
公开号：US20070238723A1
公开（公告）日：2007-10-11
Cyclopentyl compounds linked to a benzoxazinyl group through an amido moiety utilizing the ring nitrogen of the benzoxazine, and further substituted with a heterocyclic moiety, such compounds represented by formula I:
which are used to modulate the CCR-2 chemokine receptor to prevent or treat inflammatory and immunoregulatory disorders and diseases, allergic diseases, atopic conditions including allergic rhinitis, dermatitis, conjunctivitis, and asthma, as well as autoimmune pathologies such as rheumatoid arthritis and atherosclerosis; and pharmaceutical compositions comprising these compounds and the use of these compounds and compositions.
