In some countries, ibuprofen lysine (the lysine salt of ibuprofen, sometimes called "ibuprofen lysinate") is licensed for treatment of the same conditions as ibuprofen; the lysine salt is used because it is more water-soluble.
Ibuprofen lysine is being sold for rapid pain relief because, given in form of a lysine salt, absorption is much quicker (35 minutes compared to 90–120 minutes). However, a clinical trial with 351 participants in 2020, which was funded by Sanofi, found that there is no significant difference between ibuprofen and ibuprofen lysine concerning the eventual onset of action or analgesic efficacy.[unreliable medical source]
In 2006, ibuprofen lysine was approved in the U.S. by the Food and Drug Administration (FDA) for closure of patent ductus arteriosus in premature infants weighing between 500 and 1,500 g (1 and 3 lb), who are no more than 32 weeks' gestational age when usual medical management (such as fluid restriction, diuretics, and respiratory support) is not effective.
Allergic reactions, including anaphylaxis and anaphylactic shock, may occur. Ibuprofen may be quantified 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 people who are hospitalized, or assist in a medicolegal death investigation. A monograph relating ibuprofen plasma concentration, time since ingestion, and risk of developing renal toxicity in people who have overdosed has been published.
In October 2020, the U.S. Food and Drug Administration (FDA) required the drug label to be updated for all nonsteroidal anti-inflammatory medications to describe the risk of kidney problems in unborn babies that result in low amniotic fluid. They recommend avoiding NSAIDs in pregnant women at 20 weeks or later in pregnancy.
According to the Food and Drug Administration (FDA), "ibuprofen can interfere with the antiplatelet effect of low-dose aspirin, potentially rendering aspirin less effective when used for cardioprotection and stroke prevention". Allowing sufficient time between doses of ibuprofen and immediate-release (IR) aspirin can avoid this problem. The recommended elapsed time between a 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 IR aspirin, and 8 hours or more for ibuprofen taken before IR 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.
Ibuprofen combined with paracetamol is considered generally safe in children for short-term usage.
Correlation between severity of symptoms and measured ibuprofen plasma levels is weak. Toxic effects are unlikely at doses below 100mg/kg, but can be severe above 400mg/kg (around 150 tablets of 200mg units for an average man); however, large doses do not indicate the clinical course is likely to be lethal. A precise lethal dose is difficult to determine, as it may vary with age, weight, and concomitant conditions of the individual person.
Treatment to address an ibuprofen overdose is based on how the symptoms present. In cases presenting early, decontamination of the stomach is recommended. This is achieved using activated charcoal; charcoal adsorbs the drug before it can enter the bloodstream. 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. Purposeful vomiting is not recommended. 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 kidney function monitored. 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, the kidneys' excretion of unchanged drug is minimal. Forced alkaline diuresis is, therefore, of limited benefit.
A study of pregnant women suggests that those taking any type or amount of NSAIDs (including ibuprofen, diclofenac and naproxen) were 2.4 times more likely to miscarry than those not taking the medications. However, an Israeli study found no increased risk of miscarriage in the group of mothers using NSAIDs.
Like aspirin and indomethacin, ibuprofen is a nonselective COX inhibitor, in that it inhibits two isoforms of cyclooxygenase, COX-1 and COX-2. The analgesic, antipyretic, and anti-inflammatory activity of NSAIDs appears to operate mainly through inhibition of COX-2, which decreases the synthesis of prostaglandins involved in mediating inflammation, pain, fever, and swelling. Antipyretic effects may be due to action on the hypothalamus, resulting in an increased peripheral blood flow, vasodilation, and subsequent heat dissipation. Inhibition of COX-1 instead would be responsible for unwanted effects on the gastrointestinal tract. 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.
Ibuprofen is administered as a racemic mixture. The R-enantiomer undergoes extensive interconversion to the S-enantiomer in vivo. The S-enantiomer is believed to be the more pharmacologically active enantiomer. The R-enantiomer is converted through a series of three main enzymes. These enzymes include acyl-CoA-synthetase, which converts the R-enantiomer to (−)-R-ibuprofen I-CoA; 2-arylpropionyl-CoA epimerase, which converts (−)-R-ibuprofen I-CoA to (+)-S-ibuprofen I-CoA; and hydrolase, which converts (+)-S-ibuprofen I-CoA to the S-enantiomer. In addition to the conversion of ibuprofen to the S-enantiomer, the body can metabolize ibuprofen to several other compounds, including numerous hydroxyl, carboxyl and glucuronyl metabolites. Virtually all of these have no pharmacological effects.
Unlike most other NSAIDs, ibuprofen also acts as an inhibitor of Rho kinase and may be useful in recovery from spinal-cord injury.
After oral administration, peak serum concentration is reached after 1–2 hours, and up to 99% of the drug is bound to plasma proteins. The majority of ibuprofen is metabolized and eliminated within 24 hours in the urine; however, 1% of the unchanged drug is removed through biliary excretion.
The original synthesis of ibuprofen by the Boots Group started with the compound 2-methylpropylbenzene. The synthesis took six steps. A modern, greener technique for the synthesis involves only three steps.
Ibuprofen was derived from propionic acid by the research arm of Boots Group during the 1960s. The name is derived from the 3 functional groups: isobutyl (ibu) propionic acid (pro) phenyl (fen). Its discovery was the result of research during the 1950s and 1960s to find a safer alternative to aspirin. The molecule was discovered and synthesized by a team led by Stewart Adams, with a patent application filed in 1961. Adams initially tested the drug as treatment for his hangover.
In recognition of the work during the 1980s by The Boots Company PLC on the development of ibuprofen which resulted in its move from prescription only status to over the counter sale, therefore expanding its use to millions of people worldwide
In recognition of the pioneering research work, here on Pennyfoot Street, by Dr Stewart Adams and Dr John Nicholson in the Research Department of Boots which led to the discovery of ibuprofen used by millions worldwide for the relief of pain.
Ibuprofen was made available under prescription in the United Kingdom in 1969, and in the United States in 1974. In the years since, the good tolerability profile, along with extensive experience in the population, as well as in so-called phase-IV trials (postapproval studies), have resulted in the availability of ibuprofen OTC in pharmacies worldwide, as well as in supermarkets and other general retailers.
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. 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. 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 paracetamol. 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.
Ibuprofen is being researched in Córdoba, Argentina as a treatment for COVID‑19, using it in a hypertonic solution and inhaling it. The clinical trials started in June 2020. There is no validated (peer-reviewed) publication showing the effectiveness of ibuprofen in treatment of COVID‑19, nor is there any evidence that it blocks SARS-CoV-2 infectivity in any test, either on cultured cells or in animals. The only publication from the Argentine group is in the controversial journal "Medical Hypotheses" and contains no data of any sort on the effectiveness of ibuprofen. It simply makes a hypothetical suggestion, based primarily on data from other viruses that are very different from SARS-CoV-2.
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