이부프로펜 C화학적 특성, 용도, 생산
화학적 성질
Colourless, Crystalline Solid
역사
Ibuprofen
was developed while searching for an alternative pain reliever to aspirin in the 1950s. It and
related compounds were synthesized in 1961 by Stewart Adams, John Nicholson, and Colin
Burrows who were working for the Boots Pure Drug Company in Great Britain. Adams and
Nicholson filed for a British patent on ibuprofen in 1962 and obtained the patent in 1964;
subsequent patents were obtained in the United States. The patent of Adams and Nicholson
was for the invention of phenylalkane derivatives of the form shown in Figure 49.1, where
R1 could be various alkyl groups, R2 was hydrogen or methyl, and X was COOH or COOR,
with R being alkyl or aminoalkyl groups. The first clinical trials for ibuprofen were started in
1966. Ibuprofen was introduced under the trade name Brufen in 1969 in Great Britain. It was
introduced in the United States in 1974. Ibuprofen was initially off ered by prescription, but
it became available in over-the-counter medications in the 1980s.
용도
A common goal in the development of pain and inflammation medicines has been the creation of compounds that have the ability to treat inflammation, fever, and pain without disrupting other physiological functions. General pain relievers, such as aspirin and ibuprofen, inhibit both COX-1 and COX-2. A medication's specificaction toward COX-1 versus COX-2 determines the potential for adverse side effects. Medications with greater specificity toward COX-1 will have greater potential for producing adverse side effects. By deactivating COX-1, nonselective pain relievers increase the chance of undesirable side effects, especially digestive problems such as stomach ulcers and gastrointestinal bleeding. COX-2 inhibitors, such as Vioxx and Celebrex, selectively deactivate COX-2 and do not aff ect COX-1 at prescribed dosages. COX-2 inhibitors are widely prescribed for arthritis and pain relief. In 2004, the Food and Drug Administration (FDA) announced that an increased risk of heart attack and stroke was associated with certain COX-2 inhibitors. This led to warning labels and voluntary removal of products from the market by drug producers; for example, Merck took Vioxx off the market in 2004. Although ibuprofen inhibits both COX-1 and COX-2, it has several times the specificity toward COX-2 compared to aspirin, producing fewer gastrointestinal side effects.
정의
ChEBI: A monocarboxylic acid that is propionic acid in which one of the hydrogens at position 2 is substituted by a 4-(2-methylpropyl)phenyl group.
Indications
Ibuprofen (Advil, Motrin) is used as an analgesic
and antipyretic as well as a treatment for rheumatoid
arthritis and degenerative joint disease. The most frequently
observed side effects are nausea, heartburn,
epigastric pain, rash, and dizziness. Incidence of GI side
effects is lower than with indomethacin.Visual changes
and cross-sensitivity to aspirin have been reported.
Ibuprofen inhibits COX-1 and COX-2 about equally. It
decreases platelet aggregation, but the duration is
shorter and the effect quantitatively lower than with aspirin.
Ibuprofen prolongs bleeding times toward high
normal value and should be used with caution in patients
who have coagulation deficits or are receiving anticoagulant
therapy.
World Health Organization (WHO)
Ibuprofen, a non-steroidal anti-inflammatory agent, was
introduced in 1969. It was approved for sale without prescription in packages
containing no more than 400 mg, in the United Kingdom in 1983. This action was
followed by the USA, Canada and several European countries. Since this time
reports of suspected adverse effects have increased. Most of these relate to gastrointestinal
disturbances, hypersensitivity reactions but aseptic meningitis, skin
rashes and renal damage have been recorded.
일반 설명
Ibuprofen, 2-(4-isobutylphenyl)propionic acid (Motrin,Advil, Nuprin), was introduced into clinical practice followingextensive clinical trials. It appears to have comparableefficacy to aspirin in the treatment of RA, but with a lowerincidence of side effects. It has also been approved for usein the treatment of primary dysmenorrhea, which is thoughtto be caused by an excessive concentration of PGs and endoperoxides. However, a recent study indicates that concurrentuse of ibuprofen and aspirin may actually interferewith the cardioprotective effects of aspirin, at least in patientswith established cardiovascular disease. This is becauseibuprofen can reversibly bind to the platelet COX-1isozymes, thereby blocking aspirin’s ability to inhibit TXA2synthesis in platelets.
Pharmacokinetics
Ibuprofen is rapidly absorbed on oral administration, with peak plasma levels being generally attained within 2 hours
and a duration of action of less than 6 hours. As with most of these acidic NSAIDs, ibuprofen (pKa = 4.4) is
extensively bound to plasma proteins (99%) and will interact with other acidic drugs that are protein bound.
Clinical Use
Ibuprofen is indicated for the relief of the signs and symptoms of rheumatoid arthritis and osteoarthritis, the relief of
mild to moderate pain, the reduction of fever, and the treatment of dysmenorrhea.
환경귀착
Ibuprofen has a high water solubility and low volatility, which
suggest a high mobility in the aquatic environment. This makes
it a commonly detected chemical of the pharmaceutical and
personal care products (PPCPs) in the environment. It is not as
persistent, however, as many other chemicals. Ibuprofen
undergoes photodegradation with exposure to direct and
indirect sunlight, although degradation products can have
effects on aquatic environments.
신진 대사
Metabolism occurs rapidly, and the drug is nearly completely excreted in the urine as unchanged drug and oxidative
metabolites within 24 hours following administration. Metabolism by CYP2C9 (90%) and CYP2C19 (10%)
involves primarily ω-, and ω1-, and ω2-oxidation of the p-isobutyl side chain, followed by alcohol oxidation of the primary alcohol resulting from ω–oxidation to the corresponding carboxylic acid. All metabolites are inactive. When
ibuprofen is administered as the individual enantiomers, the major metabolite isolated is the S-(+)-enantiomer
whatever the configuration of the starting enantiomer. Interestingly, the R-(–)-enantiomer is inverted to the
S-(+)-enantiomer in vivo via an acetyl–coenzyme A intermediate, accounting for the observation that the two
enantiomers are bioequivalent in vivo. This is a metabolic phenomenon that also has been observed for other
arylpropionic acids, such as ketoprofen, benoxaprofen, fenoprofen, and naproxen.
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