Henry's Law constant = 6.8X10-15 atm-cu m/mol at 25 °C (est)
稳定性/保质期：
Solutions of phenylephrine hydrochloride that have been diluted in 5% dextrose injection are stable for at least 48 hours at pH 3.5-7.5. /Phenylephrine hydrochloride/
Phenylephrine is mainly metabolized by monoamine oxidase A, monoamine oxidase B, and SULT1A3. The major metabolite is the inactive meta-hydroxymandelic acid, followed by sulfate conjugates. Phenylephrine can also be metabolized to phenylephrine glucuronide.
Phenylephrine undergoes extensive metabolism in the intestinal wall (first-pass) and in the liver. The principal routes of metabolism involve sulfate conjugation (primarily in the intestinal wall) and oxidative deamination (by monoamine oxidase (MAO)); glucuronidation also occurs to a lesser extent.
7-3H-phenylephrine was given to 15 volunteers by a short-infusion n = 4) or p.o. (10 volunteers, 1 patient with porto-caval anastomosis). Analysis of serum for free 3H-phenylephrine and fractionation of urinary radioactivity was performed by ion-exchange and thin-layer chromatography. ... Metabolism to phenolic conjugates mainly after oral ingestion, and to m-hydroxymandelic acid after i.v. injection, again demonstrated that m-hydroxylated amines are predominantly conjugated during the "first-pass" metabolism.
Phenylephrine has known human metabolites that include (2S,3S,4S,5R)-3,4,5-trihydroxy-6-[3-[(1R)-1-hydroxy-2-(methylamino)ethyl]phenoxy]oxane-2-carboxylic acid.
◉ Summary of Use during Lactation:The oral bioavailability of phenylephrine is only about 40%,[1] so the drug is unlikely to reach the infant in large amounts. However, intravenous or oral administration of phenylephrine might decrease milk production. Because no information is available on the use of oral phenylephrine during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.
Phenylephrine nasal spray or ophthalmic drops are less likely to decrease lactation. To substantially diminish the effect of the drug after using eye drops, place pressure over the tear duct by the corner of the eye for 1 minute or more, then remove the excess solution with an absorbent tissue.
◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk:Relevant published information in humans was not found as of the revision date. However, animal data indicate that phenylephrine can decrease milk production[2][3] and pseudoephedrine, a pharmacologically similar vasoconstrictor, decreases milk production in nursing mothers after oral use.[4]
◈ What is phenylephrine?
Phenylephrine is a decongestant. Decongestants are often in over-the-counter medications used to treat nasal congestion (“stuffy nose”) caused by colds or allergies. Phenylephrine can be found in different products, including Sudafed PE. Phenylephrine has also been used to treat temporary low blood pressure caused by anesthesia used during surgeries.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. If you use a decongestant, it may be best to choose one that has only one active ingredient (not one with many active ingredients). This avoids exposing the pregnancy to other medications that may not be needed. Your healthcare providers can talk with you about the benefits of treating your condition and the risks of untreated illness during pregnancy.
◈ I take phenylephrine. Can it make it harder for me to get pregnant?
It is not known if phenylephrine can make it harder to get pregnant.
◈ Does taking phenylephrine increase the chance for miscarriage?
Miscarriage can occur in any pregnancy. Studies have not been done to see if phenylephrine increases the chance for miscarriage.
◈ Does taking phenylephrine 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, it is not known if phenylephrine increases the chance for birth defects above the background risk.Studies involving more than 1,500 people who were pregnant and took phenylephrine in the first trimester did not show an increased chance for birth defects. One study looked at 1,249 people who were pregnant and who took phenylephrine in the first trimester. A slightly higher chance for minor differences of the eyes or ears were reported (small changes that are not birth defects). Studies on other medications that work in the same way (make blood vessels smaller) have raised questions about a small increased chance for birth defects.
◈ Does taking phenylephrine in pregnancy increase the chance of other pregnancy-related problems?
Based on the studies reviewed, it is not known if phenylephrine can cause other 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). Because phenylephrine can make blood vessels smaller (constrict), there are theoretical concerns that using this medication could reduce blood flow through the placenta (organ that grows during pregnancy to supply the developing baby with food and oxygen).Because phenylephrine can constrict blood vessels, using this medication could raise your blood pressure. If you have high blood pressure, talk to your healthcare provider about medications that would be best for you.
◈ Does taking phenylephrine in pregnancy affect future behavior or learning for the child?
Studies have not been done to see if phenylephrine can cause behavior or learning issues for the child.
◈ Breastfeeding while taking phenylephrine:
Studies have not been done to see if phenylephrine gets into breastmilk. Studies in animals have shown that phenylephrine might reduce milk supply. Because there is little information about the use of phenylephrine while breastfeeding, use of nasal sprays or other medication might be preferred.
◈ If a male takes phenylephrine, could it affect fertility (ability to get partner pregnant) or increase the chance of birth defects?
Studies have not been done to see if phenylephrine could affect fertility or increase the chance of birth defects above the background risk. 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/.
Administration of a 10% solution of phenylephrine hydrochloride to patients pretreated with 2% pilocarpine hydrochloride produces mydriasis but to a lesser degree than occurs in patients who are not receiving the miotic. Pilocarpine may prevent or reduce visual disturbances and the risk of increased intraocular pressure associated with mydriasis in some patients and may be used to hasten recovery from mydriasis after ophthalmologic examination. Phenylephrine may reduce ciliary and conjunctival congestion and accommodative myopia often encountered when miotics are used alone in the treatment of glaucoma, without compromising the effectiveness of glaucoma therapy.
Concomitant administration of phenylephrine with cycloplegic antimuscarinic drugs such as atropine sulfate, cyclopentolate hydrochloride, homatropine hydrobromide, or scopolamine hydrobromide produces increased dilation of the pupil which is of clinical value.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
相互作用
应该考虑到洋地黄可能会增强心肌对拟交感神经药物的反应。
The possibility that digitalis can sensitize the myocardium to the effects of sympathomimetic drugs should be considered.
Phenylephrine is 38% orally bioavailable. Clinically significant systemic absorption of ophthalmic formulations is possible, especially at higher strengths and when the cornea is damaged.
86% of a dose of phenylephrine is recovered in the urine with 16% as the unmetabolized drug, 57% as the inactive meta-hydroxymendelic acid, and 8% as inactive sulfate conjugates.
来源:DrugBank
吸收、分配和排泄
分布容积
苯肾上腺素的分布容积为340升。
The volume of distribution of phenylephrine is 340L.
来源:DrugBank
吸收、分配和排泄
清除
苯肾上腺素的平均清除率为2100毫升/分钟。
Phenylephrine has an average clearance of 2100mL/min.
Phenylephrine undergoes rapid distribution into peripheral tissues; there is some evidence that the drug may be stored in certain organ compartments. The pharmacologic effects of phenylephrine are terminated at least partially by uptake of the drug into tissues. Penetration of phenylephrine into the brain appears to be minimal. Phenylephrine does not appear to be distributed to any great extent into breast milk.
Purification and characterization of a novel carbonyl reductase involved in oxidoreduction of aromatic β-amino ketones/alcohols
摘要：
Aromatic beta-amino ketones/alcohols such as adrenalone play an important role in some stereoselective synthesis of pharmaceuticals. Unfortunately, the transformation of aromatic beta-amino ketones to their chiral alcohols has been carried out chemically as no corresponding biocatalyst has been available. Here, a novel carbonyl reductase responsible for the reduction of adrenalone to (R)-(-)-epinephrine was identified and characterized from Kocuria rhizophila. This enzyme was purified to homogeneity by ammonium sulfate precipitation followed by ion-exchange column chromatography, hydrophobic chromatography and gel chromatography. The purified enzyme yielded pure (R)-enantiomer product with high activity and utilized NADH as the cofactor. The enzyme had special significance by showing selectivity for many aromatic beta-amino ketones/alcohols such as 2-amino-acetophenone, 2-amino-4'-hydroxyacetophenone, isoproterenol and ephedrine. The maximum reaction rate (V-max) and apparent Michaelis-Menten constant (K-m) for adrenalone and NADH were 14.62 mu mol/(min mg) protein and 0.189 mM, 11.66 mu mol/(min mg) protein and 0.204 mM respectively. These properties ensure the enzyme a promising future for industrial application as a replacement of chemical synthesis of aromatic beta-amino chiral alcohols. (C) 2014 Elsevier Ltd. All rights reserved.
[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.
[EN] KINASE INHIBITORS FOR THE TREATMENT OF DISEASE<br/>[FR] INHIBITEURS DE KINASE POUR LE TRAITEMENT D'UNE MALADIE
申请人：DANA FARBER CANCER INST INC
公开号：WO2015006492A1
公开（公告）日：2015-01-15
The invention relates to compounds and their use in the treatment of disease. Novel irreversible inhibitors of wild-type and mutant forms of EGFR, FGFR, ALK, ROS, JAK, BTK, BLK, ITK, TEC, and/or TXK and their use for the treatment of cell proliferation disorders are described.
