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Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) widely marketed under various trademarks including Act-3, Advil, Brufen, Motrin, Nuprin, and Nurofen. It is used for relief of symptoms of arthritis, primary dysmenorrhoea, and fever; and as an analgesic, especially where there is an inflammatory component. Ibuprofen was developed by the research arm of Boots Group.

Clinical use

Low doses of ibuprofen (200 mg, and sometimes 400 mg) are available over the counter (OTC) in most countries. Ibuprofen has a dose-dependent duration of action of approximately 4–8 hours, which is longer than suggested by its short half-life. The recommended dose varies with body mass and indication. Generally, the oral dose is 200–400 mg (5–10 mg/kg in children) every 4–6 hours, up to a usual maximum daily dose of 800–1200 mg. Under medical direction, a maximum daily dose of 3200 mg may sometimes be used.
Ibuprofen Drug

Off-Label and investigational use
As with other NSAIDs, ibuprofen may be useful in the treatment of severe orthostatic hypotension (PMID 7041104)
In some studies, ibuprofen showed superior results compared to placebo in the prophylaxis of Alzheimer's disease, when given in low doses over a long time (PMID 16195368). 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 Parkinson's disease. Aspirin, other NSAIDs, and acetaminophen had no effect on the risk for Parkinson's (PMID 16240369). Further research is warranted before recommending ibuprofen for this use.

Ibuprofen lysine
In Europe and Australia, ibuprofen lysine (ibuprofenlysinat, the lysine salt of ibuprofen) is licensed for treatment of the same conditions as ibuprofen. Ibuprofen lysine is said to have a more rapid onset of action compared to base ibuprofen.

Mechanism of action
Ibuprofen is an NSAID which is believed to work through inhibition of cyclooxygenase (COX); thus inhibiting prostaglandin synthesis. As with other NSAIDs, ibuprofen inhibits platelet aggregation, but is not used therapeutically for this action since it is a minor and reversible effect.

Main article: Non-steroidal anti-inflammatory drug

Adverse effects
Ibuprofen appears to have the lowest incidence of gastrointestinal adverse drug reactions (ADRs) of all the non-selective NSAIDs. However, this only holds true at lower doses of ibuprofen, so over-the-counter preparations of ibuprofen are generally labelled to advise a maximum daily dose of 1,200 mg.

Main article: Non-steroidal anti-inflammatory drug

Reported adverse drug reaction
In low single doses (200 to 400 mg) and daily doses of up to 1,200 mg the incidence of side effects is low. However, in patients treated on a long-term basis with more than 1,200 mg daily discontinuation rates are as high as 10 to 15%.

Common adverse effects include: nausea, dyspepsia, gastrointestinal ulceration/bleeding, raised liver enzymes, diarrhoea, headache, dizziness, salt and fluid retention, hypertension (Rossi, 2004).

Infrequent adverse effects include: oesophageal ulceration, heart failure, hyperkalaemia, renal impairment, confusion, bronchospasm, rash (Rossi, 2004)

As with other NSAIDs, ibuprofen has been reported to be a photosensitising agent. (Castell et al., 1987) Ibuprofen, however, has a very weak absorption spectrum which does not reach into the solar spectrum. The molecule contains only a single phenyl moiety, and no bond conjugation, resulting in a very weak chromophore system. Ibuprofen, therefore, is only a very weak photosensitising agent when compared with other members of the 2-arylpropionic acids.

Cardiovascular risk
Along with several other NSAIDs, ibuprofen has been implicated in elevating the risk of myocardial infarction, particularly among those chronically using high doses. (Hippisley-Cox & Coupland, 2005)

Ibuprofen, like other 2-arylpropionate derivatives (including ketoprofen, flurbiprofen, naproxen, etc) contains a chiral carbon 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 it was found that (S)-(+)-ibuprofen (dexibuprofen) was 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 which converted (R)-ibuprofen to the active (S)-enantiomer. Thus, due to the expense and futility that might be involved in marketing the single-enantiomer, all ibuprofen formulations currently marketed are a racemic mixture of both enantiomers.

Human toxicology
Only limited experience in human overdose exists. Usually, the severity of symptoms varies with the ingested dose and the time elapsed. However, individual sensitivity plays an important role. 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 qualities of ibuprofen and include abdominal pain, nausea, emesis, drowsiness, dizziness, and nystagmus. Gastrointestinal bleeding is possible. In addition other adverse effects such as headache, tinnitus, central nervous depression, seizures, hypotension, bradycardia, tachycardia, and atrial fibrillation may occur. Rarely have been reported : metabolic acidosis, coma, acute renal failure, fluid and sodium retention with edema, hyperkalema, apnea (chiefly in young children), respiratory depression, and respiratory arrest. Cyanosis has been seen in a few cases. Generally, the symptoms observed with an overdose of ibuprofen are similar to the symptoms caused by overdoses of other NSAIDs.

Little correlation between severity of symptoms of overdose and measured plasma levels exist. Critical doses are between approximately 100 mg/kg and 800 mg/kg; the latter dose does not indicate that the clinical course is lethal in any case. A therapeutical single dose is 5 to 10 mg/kg. Therefore the therapeutic index varies between 10 and 160; but it is not possible to determine a precise LD50, as the lethal dose varies with age, weight, and concomitant diseases of the individual patient.

Therapy is largely symptomatic. In early cases emesis should be induced. Also, gastric lavage can be beneficial. In any case activated charcoal should be administered repeatedly to absorb the drug before it can enter the systemic circulation. Standard measures to maintain normal urine output should be instituted. Since ibuprofen has acidic properties and is also excreted in the urine, forced alkaline diuresis may be useful. Symptomatic therapy of hypotension, GI bleeding, and acidosis may also be indicated. Usually, close monitoring in an intensive care unit for several days is indicated and necessary. If a patient survives the acute intoxication, he/she will usually experience no late sequelae.

Ibuprofen was made available under prescription in the United Kingdom in 1969. In the years since, the good tolerability profile along with extensive experience in the community (otherwise known as Phase IV trials), has resulted in the rescheduling of small packs of ibuprofen to allow availability over-the-counter in pharmacies worldwide. Indeed there has been an increasing trend towards descheduling ibuprofen such that it is now available in supermarkets and other general retailers; in fact, in the United States, ibuprofen (most commonly in a 200 mg dosage) is about as widely used as aspirin and acetaminophen as an over-the-counter painkiller.

Slang names
A standing joke about some athletes' regular use has produced "Vitamin I" as a slang term for ibuprofen.

In the military, "Grunt Candy" is used as a generic name for Ibuprofen, Acetaminophen, or Naproxen.

AHFS online
Rossi S (Ed.) (2004). Australian Medicines Handbook 2004. Adelaide: Australian Medicines Handbook. ISBN 0-9578521-4-2.
Castell JV, Gomez MJ, Miranda MA, Morera IM (1987). Photolytic degradation of ibuprofen. Toxicity of the isolated photoproducts on fibroblasts and erythrocytes. Photochem Photobiol 46 (6), 991-6.
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. British Medical Journal 2005;330:1366 (11 June).

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