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It was logical, then, that there was the potential for improving the selectivity and potency of ibuprofen formulations by marketing ibuprofen as a single-enantiomer product (as occurs with [[naproxen]], another NSAID).
It was logical, then, that there was the potential for improving the selectivity and potency of ibuprofen formulations by marketing ibuprofen as a single-enantiomer product (as occurs with [[naproxen]], another NSAID).


Further ''in vivo'' testing, however, revealed the existence of an [[isomerase]] (''alpha-methylacyl-CoA racemase''), which converted (''R'')-ibuprofen to the active (''S'')-[[enantiomer]].<ref>{{Cite journal|doi=10.1016/0167-4838(91)90164-U|author=Chen CS, Shieh WR, Lu PH, Harriman S, Chen CY |title=Metabolic stereoisomeric inversion of ibuprofen in mammals |journal=Biochim Biophys Acta |volume=1078 |issue=3 |pages=411–7 |year=1991 |pmid=1859831 }}</ref><ref>{{Cite journal|author=Tracy TS, Hall SD |title=Metabolic inversion of (''R'')-ibuprofen. Epimerization and hydrolysis of ibuprofenyl-coenzyme A |journal=Drug Metab Dispos |volume=20 |issue=2 |pages=322–7 |year=1992 |pmid=1352228 |doi=}}</ref><ref>{{Cite journal|author=Reichel C, Brugger R, Bang H, Geisslinger G, Brune K |title=Molecular cloning and expression of a 2-arylpropionyl-coenzyme A epimerase: a key enzyme in the inversion metabolism of ibuprofen |journal=Mol Pharmacol |volume=51 |issue=4 |pages=576–82 |year=1997 |pmid=9106621 |url=http://molpharm.aspetjournals.org/cgi/content/full/51/4/576}}</ref> Due to the expense and probable futility of making pure (''S'')-(+)-ibuprofen, most ibuprofen formulations currently marketed are [[Racemic|racemic mixtures]].{{citation needed|date=March 2011}}
Further ''in vivo'' testing, however, revealed the existence of an [[isomerase]] (''[[alpha-methylacyl-CoA racemase]]''), which converted (''R'')-ibuprofen to the active (''S'')-[[enantiomer]].<ref>{{Cite journal|doi=10.1016/0167-4838(91)90164-U|author=Chen CS, Shieh WR, Lu PH, Harriman S, Chen CY |title=Metabolic stereoisomeric inversion of ibuprofen in mammals |journal=Biochim Biophys Acta |volume=1078 |issue=3 |pages=411–7 |year=1991 |pmid=1859831 }}</ref><ref>{{Cite journal|author=Tracy TS, Hall SD |title=Metabolic inversion of (''R'')-ibuprofen. Epimerization and hydrolysis of ibuprofenyl-coenzyme A |journal=Drug Metab Dispos |volume=20 |issue=2 |pages=322–7 |year=1992 |pmid=1352228 |doi=}}</ref><ref>{{Cite journal|author=Reichel C, Brugger R, Bang H, Geisslinger G, Brune K |title=Molecular cloning and expression of a 2-arylpropionyl-coenzyme A epimerase: a key enzyme in the inversion metabolism of ibuprofen |journal=Mol Pharmacol |volume=51 |issue=4 |pages=576–82 |year=1997 |pmid=9106621 |url=http://molpharm.aspetjournals.org/cgi/content/full/51/4/576}}</ref> Due to the expense and probable futility of making pure (''S'')-(+)-ibuprofen, most ibuprofen formulations currently marketed are [[Racemic|racemic mixtures]].{{citation needed|date=March 2011}}


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Revision as of 14:23, 21 May 2011

Ibuprofen
Clinical data
License data
Pregnancy
category
  • AU: C
Routes of
administration		Oral, rectal, topical, and intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability49–73%
Protein binding99%
MetabolismHepatic (CYP2C9)
Elimination half-life1.8–2 h
ExcretionRenal
Identifiers
  • (RS)-2-(4-(2-methylpropyl)phenyl)propanoic acid
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.036.152 Edit this at Wikidata
Chemical and physical data
FormulaC13H18O2
Molar mass206.29 g/mol g·mol−1
3D model (JSmol)
Melting point76 °C (169 °F)
  • CC(C)Cc1ccc(cc1)C(C)C(=O)O
  • InChI=1S/C13H18O2/c1-9(2)8-11-4-6-12(7-5-11)10(3)13(14)15/h4-7,9-10H,8H2,1-3H3,(H,14,15) checkY
  • Key:HEFNNWSXXWATRW-UHFFFAOYSA-N checkY
  (verify)
Coated 200 mg ibuprofen tablets

Ibuprofen (INN) (/[invalid input: 'icon']ˈaɪbjuːproʊfɛn/ or /aɪbjuːˈproʊfən/ EYE-bew-PROH-fən; from the now-outdated nomenclature iso-butyl-propanoic-phenolic acid) is a nonsteroidal anti-inflammatory drug (NSAID) used for relief of symptoms of arthritis, fever,[2] as an analgesic for pain, especially where there is an inflammatory component, and dysmenorrhea.

Ibuprofen is known to have an antiplatelet effect, though it is relatively mild and short-lived when compared with aspirin or other better-known antiplatelet drugs. In general, ibuprofen also acts as a vasodilator, having been shown to dilate coronary arteries and some other blood vessels. Ibuprofen is a core medicine in the World Health Organization's "WHO Model List of Essential Medicines", which is a list of minimum medical needs for a basic healthcare system.[3][4][5][6]

Originally marketed as Brufen, ibuprofen is available under a variety of popular trademarks, including Motrin, Nurofen, Advil, and Nuprin.[7]

Medical uses

Ibuprofen is used primarily for fever, pain, dysmenorrhea and inflammatory diseases such as rheumatoid arthritis.[8] It is also used for pericarditis and patent ductus arteriosus.[8]

Dosage

Ibuprofen has a dose-dependent duration of action of approximately four to eight hours, which is longer than suggested by its short half-life. The recommended dose varies with body mass and indication. 1,200 mg is considered the maximum daily dose for OTC use, though, under medical direction, the maximum amount of ibuprofen for adults is 800 milligrams per dose or 3200 mg per day.[citation needed]

Unlike aspirin, which breaks down in solution, ibuprofen is stable, and, thus, ibuprofen can be available in topical gel form, which is absorbed through the skin, and can be used for sports injuries, with less risk of digestive problems.[9]

Ibuprofen lysine

In Europe, Australia, and New Zealand, ibuprofen lysine (the lysine salt of ibuprofen, sometimes called "ibuprofen lysinate" even though the lysine is in cationic form) is licensed for treatment of the same conditions as ibuprofen. The lysine salt increases water solubility, allowing the medication to be administered intravenously.[10] Ibuprofen lysine has been shown to have a more rapid onset of action compared to acid ibuprofen.[11]

Ibuprofen lysine is indicated for closure of a patent ductus arteriosus in premature infants weighing between 500 and 1,500 grams (1 and 3 lb), who are no more than 32 weeks gestational age when usual medical management (e.g., fluid restriction, diuretics, respiratory support, etc.) is ineffective.[10] With regard to this indication, ibuprofen lysine is an effective alternative to intravenous indomethacin, and may be advantageous in terms of renal function.[12]

Adverse effects

Common adverse effects include: nausea, dyspepsia, gastrointestinal ulceration/bleeding, raised liver enzymes, diarrhea, constipation, epistaxis, headache, dizziness, priapism, rash, salt and fluid retention, and hypertension.[13] A study from 2010 has shown regular use of NSAIDs was associated with an increase in hearing loss.[14]

Infrequent adverse effects include: esophageal ulceration, heart failure, hyperkalemia, renal impairment, confusion, and bronchospasm.[13]

Ibuprofen appears to have the lowest incidence of digestive adverse drug reactions (ADRs) of all the nonselective NSAIDs. However, this holds true only at lower doses of ibuprofen, so OTC preparations of ibuprofen are, in general, labeled to advise a maximum daily dose of 1,200 mg.[15][16]

Photosensitivity

As with other NSAIDs, ibuprofen has been reported to be a photosensitising agent.[17][18] However, this only rarely occurs with ibuprofen and it is considered to be a very weak photosensitising agent when compared with other members of the 2-arylpropionic acid class. This is because the ibuprofen molecule contains only a single phenyl moiety and no bond conjugation, resulting in a very weak chromophore system and a very weak absorption spectrum, which does not reach into the solar spectrum[citation needed].

Cardiovascular risk

Along with several other NSAIDs, ibuprofen has been implicated in elevating the risk of myocardial infarction (heart attack), in particular, among those chronically using high doses. [19]

Interaction with aspirin

According to the U.S. Food and Drug Administration, "Ibuprofen can interfere with the antiplatelet effect of low-dose aspirin (81 mg per day), potentially rendering aspirin less effective when used for cardioprotection and stroke prevention." Allowing sufficient time between doses of ibuprofen and immediate release aspirin can avoid this problem. The recommended elapsed time between a 400 mg dose of ibuprofen and a dose of aspirin depends on which is taken first. It would be 30 minutes or more for ibuprofen taken after immediate release aspirin, and 8 hours or more for ibuprofen taken before immediate release aspirin. However, this timing cannot be recommended for enteric-coated aspirin. But, if ibuprofen is taken only occasionally without the recommended timing, the reduction of the cardioprotection and stroke prevention of a daily aspirin regimen is minimal.[20]

Risks in inflammatory bowel disease

Ibuprofen should not be used regularly in individuals with inflammatory bowel disease due to its ability to cause gastric bleeding and form ulceration in the gastric lining. Pain relievers such as paracetemol/acetaminophen or drugs containing codeine (which slows down bowel activity) are safer methods than ibuprofen for pain relief from IBD. Ibuprofen is also known to cause worsening of IBD during flare-ups, so it should be avoided completely at those times.[citation needed]

Overdose

Ibuprofen overdose has become common since it was licensed for OTC use. There are many overdose experiences reported in the medical literature, although the frequency of life-threatening complications from ibuprofen overdose is low.[21] Human response in cases of overdose ranges from absence of symptoms to fatal outcome in spite of intensive care treatment. Most symptoms are an excess of the pharmacological action of ibuprofen and include abdominal pain, nausea, vomiting, drowsiness, dizziness, headache, tinnitus, and nystagmus. Rarely, more severe symptoms, such as gastrointestinal bleeding, seizures, metabolic acidosis, hyperkalaemia, hypotension, bradycardia, tachycardia, atrial fibrillation, coma, hepatic dysfunction, acute renal failure, cyanosis, respiratory depression, and cardiac arrest have been reported.[22] The severity of symptoms varies with the ingested dose and the time elapsed; however, individual sensitivity also plays an important role. Generally, the symptoms observed with an overdose of ibuprofen are similar to the symptoms caused by overdoses of other NSAIDs.

There is little correlation between severity of symptoms and measured ibuprofen plasma levels. Toxic effects are unlikely at doses below 100 mg/kg, but can be severe above 400 mg/kg (around 150 tablets of 200 mg units for an average man);[23] however, large doses do not indicate the clinical course is likely to be lethal.[24] It is not possible to determine a precise lethal dose, as this may vary with age, weight, and concomitant diseases of the individual patient.

Therapy is largely symptomatic. In cases presenting early, gastric decontamination is recommended. This is achieved using activated charcoal; charcoal adsorbs the drug before it can enter the systemic circulation. Gastric lavage is now rarely used, but can be considered if the amount ingested is potentially life-threatening, and it can be performed within 60 minutes of ingestion. Emesis is not recommended.[25] The majority of ibuprofen ingestions produce only mild effects and the management of overdose is straightforward. Standard measures to maintain normal urine output should be instituted and renal function monitored.[23] Since ibuprofen has acidic properties and is also excreted in the urine, forced alkaline diuresis is theoretically beneficial. However, because ibuprofen is highly protein-bound in the blood, there is minimal renal excretion of unchanged drug. Forced alkaline diuresis is, therefore, of limited benefit.[26] Symptomatic therapy for hypotension, GI bleeding, acidosis, and renal toxicity may be indicated. On occasion, close monitoring in an intensive care unit for several days is necessary. If a patient survives the acute intoxication, he or she will usually experience no late sequelae.

Detection in body fluids

Ibuprofen may be quantitated in blood, plasma, or serum to demonstrate the presence of the drug in a person having experienced an anaphylactic reaction, confirm a diagnosis of poisoning in hospitalized patients, or assist in a medicolegal death investigation. A nomogram that relates the ibuprofen plasma concentration, time since ingestion, and risk of developing renal toxicity in overdose patients has been published.[27]

Mechanism of action

Nonsteroidal anti-inflammatory drugs such as ibuprofen work by inhibiting the enzyme cyclooxygenase (COX), which converts arachidonic acid to prostaglandin H2 (PGH2). PGH2, in turn, is converted by other enzymes to several other prostaglandins (which are mediators of pain, inflammation, and fever) and to thromboxane A2 (which stimulates platelet aggregation, leading to the formation of blood clots).

Like aspirin, indomethacin, and most other NSAIDs,[citation needed] ibuprofen is considered a nonselective COX inhibitor; that is, it inhibits two isoforms of cyclooxygenase, COX-1 and COX-2. The analgesic, antipyretic, and anti-inflammatory activity of NSAIDs appears to be achieved mainly through inhibition of COX-2, whereas inhibition of COX-1 would be responsible for unwanted effects on platelet aggregation and the gastrointestinal tract.[28] However, the role of the individual COX isoforms in the analgesic, anti-inflammatory, and gastric damage effects of NSAIDs is uncertain and different compounds cause different degrees of analgesia and gastric damage.[29] In order to achieve the beneficial effects of ibuprofen and other NSAIDS without gastrointestinal ulceration and bleeding, selective COX-2 inhibitors were developed to inhibit the COX-2 isoform without inhibition of COX-1.[30]

Chemistry

Ibuprofen is only very slightly soluble in water. Less than 1 mg of ibuprofen dissolves in 1 ml water (< 1 mg/mL).[31] However, it is much more soluble in alcohol/water mixtures as well as carbonated water.

Stereochemistry

Ibuprofen, like other 2-arylpropionate derivatives (including ketoprofen, flurbiprofen, naproxen, etc.), contains a stereocenter in the α-position of the propionate moiety. As such, there are two possible enantiomers of ibuprofen, with the potential for different biological effects and metabolism for each enantiomer.

Indeed, the (S)-(+)-ibuprofen (dexibuprofen) was found to be the active form both in vitro and in vivo.

It was logical, then, that there was the potential for improving the selectivity and potency of ibuprofen formulations by marketing ibuprofen as a single-enantiomer product (as occurs with naproxen, another NSAID).

Further in vivo testing, however, revealed the existence of an isomerase (alpha-methylacyl-CoA racemase), which converted (R)-ibuprofen to the active (S)-enantiomer.[32][33][34] Due to the expense and probable futility of making pure (S)-(+)-ibuprofen, most ibuprofen formulations currently marketed are racemic mixtures.[citation needed]

(R)-ibuprofen
(S)-ibuprofen

Synthesis

The synthesis of this compound is a popular case study in green chemistry. The original Boots synthesis of ibuprofen consisted of six steps, started with the Friedel-Crafts acetylation of isobutylbenzene. Reaction with ethyl chloroacetate (Darzens reaction) gave the α,β-epoxy ester, which was hydrolyzed and decarboxylated to the aldehyde. Reaction with hydroxylamine gave the oxime, which was converted to the nitrile, then hydrolyzed to the desired acid:[35]

An improved synthesis by BHC required only three steps. This improved synthesis won the Presidential Green Chemistry Challenge Greener Synthetic Pathways Award in 1997.[36]

After a similar acetylation, hydrogenation with Raney nickel gave the alcohol, which underwent palladium-catalyzed carbonylation:[35]

History

Ibuprofen was derived from propionic acid by the research arm of Boots Group during the 1960s.[37] It was discovered by Andrew RM Dunlop, with colleagues Stewart Adams, John Nicholson, Vonleigh Simmons, Jeff Wilson and Colin Burrows, and was patented in 1961. The drug was launched as a treatment for rheumatoid arthritis in the United Kingdom in 1969, and in the United States in 1974. Dr. Adams initially tested his drug on a hangover. He was subsequently awarded an OBE in 1987. Boots was awarded the Queen's Award For Technical Achievement for the development of the drug in 1987.[38]

Availability

See also: List of ibuprofen brand names
A bottle of generic ibuprofen

Ibuprofen was made available under prescription in the United Kingdom in 1969, and in the United States in 1974.[citation needed] In the years since, the good tolerability profile, along with extensive experience in the population, as well as in so-called Phase IV trials (post-approval studies), has resulted in the availability of ibuprofen over the counter in pharmacies worldwide, as well as in supermarkets and other general retailers.[citation needed]

Europe

For some time, there has been a limit on the quantity of ibuprofen that can be bought OTC in a single transaction in the UK. Behind the counter in pharmacies, this is one pack of 96 × 200 mg or 400 mg, the latter being far less common for OTC sales.

In Germany and Finland, 600 mg and 800 mg per pill packages have to be prescribed, whereas 400 mg is available OTC in pharmacies. In Italy, Belgium, and the Netherlands, 200 mg and 400 mg pills are available with no prescription.

In other countries, such as Spain, higher dosages of 600 mg are available.

North America

Ibuprofen is commonly available in the United States up to the FDA's 200 mg 1984 dose limit OTC, higher by prescription.[39] In Canada, the OTC dose limit is 400 mg.[citation needed]

In 2009, the first injectable formulation of ibuprofen was approved in the United States, under the trade name Caldolor.[40][41] Ibuprofen was the only parenteral for both pain and fever available in the country prior to the approval of Ofirmev (acetaminophen) injection by the FDA.[42]

Research

Ibuprofen is sometimes used for the treatment of acne, because of its anti-inflammatory properties,[43] and has been sold in Japan in topical form for adult acne.[44]

As with other NSAIDs, ibuprofen may be useful in the treatment of severe orthostatic hypotension (low blood pressure when standing up).[45]

In some studies, ibuprofen showed superior results compared to a placebo in the prophylaxis of Alzheimer's disease, when given in low doses over a long time.[46] Further studies are needed to confirm the results before ibuprofen can be recommended for this indication.

Ibuprofen has been associated with a lower risk of Parkinson's disease, and may delay or prevent it. Aspirin, other NSAIDs, and paracetamol (acetaminophen) had no effect on the risk for Parkinson's.[47] In March 2011, researchers at Harvard Medical School announced in Neurology that ibuprofen had a neuroprotective effect against the risk of developing Parkinson's disease.[48] People regularly consuming ibuprofen were reported to have a 38% lower risk of developing Parkinson's disease, but no such effect was found for other pain relievers, such as aspirin and acetaminophen. Use of ibuprofen to lower the risk of Parkinson's disease in the general population would not be problem-free, given the possibility of adverse effects on the urinary and digestive systems. In the same week, another study linked regular use of NSAIDs, including ibuprofen, to erectile dysfunction.[49] Further research is warranted before recommending ibuprofen for this use.

References

  1. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
  2. ^ Van Esch, A; Van Steensel-Moll, HA; Steyerberg, EW; Offringa, M; Habbema, JD; Derksen-Lubsen, G (1995). "Antipyretic efficacy of ibuprofen and acetaminophen in children with febrile seizures". Arch Pediatr Adolesc Med. 149 (6): 632–7. PMID 7767417. {{cite journal}}: Unknown parameter |month= ignored (help)
  3. ^ WHO Model List of Essential Medicines (PDF) (16th ed.). World Health Organization (WHO). 2009. Retrieved 2011-03-30. {{cite book}}: Unknown parameter |month= ignored (help)
  4. ^ WHO Model List of Essential Medicines for Children (PDF) (2nd ed.). World Health Organization (WHO). 2010. Retrieved 2011-03-30. {{cite book}}: Unknown parameter |month= ignored (help)
  5. ^ WHO Model Formulary 2008 (PDF) (2nd ed.). World Health Organization (WHO). 2009. ISBN 978 92 4 154765 9. Retrieved 2011-03-30. {{cite book}}: Unknown parameter |editors= ignored (|editor= suggested) (help)
  6. ^ WHO Model Formulary for Children 2010 (PDF) (2nd ed.). World Health Organization (WHO). 2010. ISBN 978 92 4 159932 0. Retrieved 2011-03-30.
  7. ^ "PubMed Health - Ibuprofen". U.S. National Library of Medicine. 2010-10-01. Retrieved 2011-01-20.
  8. ^ a b "Ibuprofen". The American Society of Health-System Pharmacists. Retrieved 3 April 2011.
  9. ^ "Topical NSAIDs: plasma and tissue concentrations". Bandolier.
  10. ^ a b Ovation Pharmaceuticals. "Neoprofen (ibuprofen lysine) injection". Package insert.
  11. ^ Geisslinger G, Dietzel K, Bezler H, Nuernberg B, Brune K (1989). "Therapeutically relevant differences in the pharmacokinetical and pharmaceutical behavior of ibuprofen lysinate as compared with ibuprofen acid". Int J Clin Pharmacol Ther Toxicol. 27 (7): 324–8. PMID 2777420.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  12. ^ Su PH, Chen JY, Su CM, Huang TC, Lee HS (2003). "Comparison of ibuprofen and indomethacin therapy for patent ductus arteriosus in preterm infants". Pediatr Int. 45 (6): 665–70. doi:10.1111/j.1442-200X.2003.01797.x. PMID 14651538.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  13. ^ a b Rossi S, ed. (2004). Australian Medicines Handbook (2004 ed.). Australian Medicines Handbook. ISBN 0-9578521-4-2. OCLC 224121065.
  14. ^ Curhan SG, Eavey R, Shargorodsky J, Curhan GC (2010). "Analgesic use and the risk of hearing loss in men". Am. J. Med. 123 (3): 231–7. doi:10.1016/j.amjmed.2009.08.006. PMC 2831770. PMID 20193831. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  15. ^ "Ibuprofen - Drug information". Medic8.com.
  16. ^ "Ibuprofen - Adverse effects". Global Oneness.
  17. ^ Bergner T, Przybilla B (1992). "Photosensitization caused by ibuprofen". J. Am. Acad. Dermatol. 26 (1): 114–6. doi:10.1016/0190-9622(92)70018-B. PMID 1531054. {{cite journal}}: Unknown parameter |month= ignored (help)
  18. ^ Thomson Healthcare. USP DI Advice for the Patient: Anti-inflammatory Drugs, Nonsteroidal (Systemic) [monograph on the internet]. Bethesda (MD): U.S. National Library of Medicine; c2006 [updated 2006 Jul 28; cited 2006 Aug 5]. MedlinePlus DrugInfo uspdi-202743
  19. ^ Hippisley-Cox J, Coupland C (2005). "Risk of myocardial infarction in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs: population based nested case-control analysis". BMJ. 330 (7504): 1366. doi:10.1136/bmj.330.7504.1366. PMC 558288. PMID 15947398.
  20. ^ "Information for Healthcare Professionals: Concomitant Use of Ibuprofen and Aspirin". U.S. Food and Drug Administration (FDA). 2006-09. Retrieved 2010-11-22. {{cite web}}: Check date values in: |date= (help)
  21. ^ McElwee NE, Veltri JC, Bradford DC, Rollins DE. (1990). "A prospective, population-based study of acute ibuprofen overdose: complications are rare and routine serum levels not warranted". Ann Emerg Med. 19 (6): 657–62. doi:10.1016/S0196-0644(05)82471-0. PMID 2188537.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  22. ^ Vale JA, Meredith TJ. (1986). "Acute poisoning due to non-steroidal anti-inflammatory drugs. Clinical features and management". Med Toxicol. 1 (1): 12–31. PMID 3537613.
  23. ^ a b Volans G, Hartley V, McCrea S, Monaghan J. (2003). "Non-opioid analgesic poisoning". Clinical Medicine. 3 (2): 119–23. doi:10.1007/s10238-003-0014-z. PMID 12737366.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  24. ^ Seifert SA, Bronstein AC, McGuire T (2000). "Massive ibuprofen ingestion with survival". J. Toxicol. Clin. Toxicol. 38 (1): 55–7. doi:10.1081/CLT-100100917. PMID 10696926.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  25. ^ American Academy Of Clinical Toxico; European Association Of Poisons Cen (2004). "Position paper: Ipecac syrup". J. Toxicol. Clin. Toxicol. 42 (2): 133–43. doi:10.1081/CLT-120037421. PMID 15214617.
  26. ^ Hall AH, Smolinske SC, Conrad FL; et al. (1986). "Ibuprofen overdose: 126 cases". Ann Emerg Med. 15 (11): 1308–13. doi:10.1016/S0196-0644(86)80617-5. PMID 3777588. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  27. ^ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 758-761.
  28. ^ Rao P, Knaus EE (2008). "Evolution of nonsteroidal anti-inflammatory drugs (NSAIDs): cyclooxygenase (COX) inhibition and beyond". J Pharm Pharm Sci. 11 (2): 81s–110s. PMID 19203472.
  29. ^ Kakuta H, Zheng X, Oda H; et al. (2008). "Cyclooxygenase-1-selective inhibitors are attractive candidates for analgesics that do not cause gastric damage. design and in vitro/in vivo evaluation of a benzamide-type cyclooxygenase-1 selective inhibitor". J. Med. Chem. 51 (8): 2400–11. doi:10.1021/jm701191z. PMID 18363350. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  30. ^ "Pain Medications". eMedicine. 2006-02-13. Retrieved 2010-06-07.
  31. ^ Motrin (Ibuprofen) drug description - FDA-approved labeling for prescription drugs and medications at RxList
  32. ^ Chen CS, Shieh WR, Lu PH, Harriman S, Chen CY (1991). "Metabolic stereoisomeric inversion of ibuprofen in mammals". Biochim Biophys Acta. 1078 (3): 411–7. doi:10.1016/0167-4838(91)90164-U. PMID 1859831.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  33. ^ Tracy TS, Hall SD (1992). "Metabolic inversion of (R)-ibuprofen. Epimerization and hydrolysis of ibuprofenyl-coenzyme A". Drug Metab Dispos. 20 (2): 322–7. PMID 1352228.
  34. ^ Reichel C, Brugger R, Bang H, Geisslinger G, Brune K (1997). "Molecular cloning and expression of a 2-arylpropionyl-coenzyme A epimerase: a key enzyme in the inversion metabolism of ibuprofen". Mol Pharmacol. 51 (4): 576–82. PMID 9106621.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  35. ^ a b "Ibuprofen — a case study in green chemistry" (PDF). Royal Society of Chemistry.
  36. ^ "Presidential Green Chemistry Challenge: 1997 Greener Synthetic Pathways Award". U.S. Environmental Protection Agency. Retrieved 2009-08-18.
  37. ^ Adams SS (1992). "The propionic acids: a personal perspective". J Clin Pharmacol. 32 (4): 317–23. PMID 1569234. {{cite journal}}: Unknown parameter |month= ignored (help)
  38. ^ Lambert, Victoria (2007-10-08). "Dr Stewart Adams: 'I tested ibuprofen on my hangover' - Telegraph". The Daily Telegraph. London. Retrieved 2008-01-20.
  39. ^ "Ibuprofen". U.S. Food and Drug Administration (FDA).
  40. ^ "Drug Approval Package: Caldolor (Ibuprofen) NDA #022348". U.S. Food and Drug Administration (FDA). March 11, 2010.
  41. ^ "FDA Approves Injectable Form of Ibuprofen" (Press release). U.S. Food and Drug Administration (FDA). June 11, 2009.
  42. ^ "FDA Approves Caldolor: Cumberland Pharmaceuticals Announces FDA Approval of Caldolor" (Press release). Drugs.com. June 11, 2009. Retrieved 2009-06-13.
  43. ^ Wong RC, Kang S, Heezen JL, Voorhees JJ, Ellis CN (1984). "Oral ibuprofen and tetracycline for the treatment of acne vulgaris". J. Am. Acad. Dermatol. 11 (6): 1076–81. doi:10.1016/S0190-9622(84)80192-9. PMID 6239884. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  44. ^ "In Japan, an OTC ibuprofen ointment (Fukidia) for alleviating adult acne has been launched". Inpharma. 1 (1530): 18. March 25, 2006.
  45. ^ Zawada, E. (1982). "Renal consequences of nonsteroidal antiinflammatory drugs". Postgrad Med. 71 (5): 223–230. PMID 7041104.
  46. ^ Townsend KP, Praticò D (2005). "Novel therapeutic opportunities for Alzheimer's disease: focus on nonsteroidal anti-inflammatory drugs" (PDF). FASEB J. 19 (12): 1592–601. doi:10.1096/fj.04-3620rev. PMID 16195368. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: unflagged free DOI (link)
  47. ^ Chen, H.; Jacobs, E.; Schwarzschild, M.; McCullough, M.; Calle, E.; Thun, M.; Ascherio, A. (2005). "Nonsteroidal antiinflammatory drug use and the risk for Parkinson's disease". Ann Neurol. 58 (6): 963–7. doi:10.1002/ana.20682. PMID 16240369.
  48. ^ Gao X, Chen H, Schwarzschild MA, Ascherio A (2011). "Use of ibuprofen and risk of Parkinson disease". Neurology. 76 (10): 863–9. doi:10.1212/WNL.0b013e31820f2d79. PMC 3059148. PMID 21368281. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  49. ^ Mary Brophy Marcus (March 2, 2011). "Ibuprofen may reduce risk of getting Parkinson's disease". USA Today.
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