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Ibuprofen
Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID)1 and a propionic acid derivative with pain-relieving, fever-reducing, and anti-inflammatory effects.1 It was discovered in 1961 by Stewart Adams and John Nicholson at Boots the Chemists. Its anti-inflammatory effects are weaker than those of other NSAIDs. It can cause gastrointestinal bleeding2 and worsen asthma or heart failure.2 Ibuprofen doses of 2,400 mg per day or higher are associated with a small increase in heart attack risk,3 and use in later pregnancy appears harmful.2
Dosage & Duration
Dosage
Doses are population estimates that vary widely between individuals.
Moderate400-800 mg
Duration
Onset1 hour
Total4-6 hours
Subjective Effects
Subjective Effects not written up yet
Pharmacology
Pharmacodynamics
Ibuprofen inhibits COX-1 and COX-2,4 reducing the production of prostaglandins and thromboxane.1 Its effects on pain, fever, and inflammation appear to depend mainly on COX-2 inhibition, although the contributions of the individual COX isoforms remain uncertain. Its analgesic action involves both peripheral tissues and central pain pathways, while reduced prostanoid signaling in the hypothalamus contributes to fever reduction. Ibuprofen inhibits sugar-induced activation of the sweet taste receptor TAS1R2-TAS1R3 in humans.5 Increased endogenous cannabinoid synthesis and effects on NMDA receptors have been proposed as additional contributors to analgesia.
Pharmacokinetics
Ibuprofen is rapidly and well absorbed from the upper gastrointestinal tract after oral administration. Peak serum concentrations occur 1-2 hours after oral or other extravascular administration; reported average exposure measurements are approximately 20 mcg/ml for Cmax, 2 hours for Tmax, and 70 mcg·h/ml for AUC, with variation by enantiomer, route, and dose. Food decreases the rate of ibuprofen absorption without changing its extent.6 Plasma protein binding is approximately 99% or greater, including binding at albumin site II; binding becomes saturable and nonlinear above 20 mcg/ml, and the apparent volume of distribution is 0.1 L/kg. Ibuprofen can enter the central nervous system.4 After absorption, 53-65% of the R-enantiomer is converted to the more active S-enantiomer through a pathway involving acyl-CoA synthetase, alpha-methylacyl-CoA racemase (2-arylpropionyl-CoA epimerase), and hydrolase. Hepatic phase I metabolism involves side-chain hydroxylation and subsequent oxidation, primarily through CYP2C9, with contributions from CYP2C19 and CYP2C8; phase II metabolism produces phenolic and acyl glucuronide conjugates. Most oxidative metabolites are inactive. More than 90% of the administered dose is eliminated through urine, predominantly after metabolism, with approximately 99% of the eliminated dose having undergone metabolism. Biliary excretion accounts for approximately 1% of the administered dose and includes unchanged drug and active phase II metabolites. Elimination is largely complete within 24 hours after the last dose.2 Serum half-life is 1.2-2 hours and can increase to 3.1-3.4 hours with impaired liver function; elimination is reported not to be impaired by older age or renal impairment. Clearance ranges from 3-13 L/h depending on route, enantiomer, and dose.
Interactions
Interactions not written up yet
An unlisted combination is an unknown one, not a safe one. Check a dedicated combination chart before mixing.
Tolerance
Tolerance not written up yet
Harm Potential
Toxicity
Toxic effects are unlikely below 100 mg/kg and can be severe above 400 mg/kg, but a large ingested dose does not by itself predict a lethal course.
LD50 Data
| Species | Route | Value |
|---|---|---|
| Rat | – | 636 mg/kg |
| Mouse | – | 740 mg/kg |
| Guinea pig | – | 495 mg/kg |
Ibuprofen can cause gastrointestinal ulceration and, infrequently, esophageal ulceration; gastrointestinal bleeding has rarely been reported in overdose.
Ibuprofen can cause infrequent kidney impairment and, rarely in overdose, acute kidney failure; use during pregnancy can impair fetal kidney function and reduce amniotic fluid.
Chronic ibuprofen use is associated with progression to hypertension in women and with myocardial infarction, particularly with chronic use of higher doses; increased stroke risk is also associated with ibuprofen.
Abnormal liver function has rarely been reported in ibuprofen overdose.
Ibuprofen can cause infrequent bronchospasm and exacerbate asthma, sometimes fatally; overdose can rarely cause respiratory depression, breathing difficulty, cyanosis, and apnea.
Ibuprofen can cause rash and is an extremely rare cause of Stevens–Johnson syndrome and toxic epidermal necrolysis.
Ibuprofen can cause allergic reactions, including anaphylaxis.8
Ibuprofen overdose can cause central nervous system depression and loss of consciousness, with coma reported rarely.9
Metabolic acidosis has rarely been reported in ibuprofen overdose.9
A study of pregnant women associated use of NSAIDs, including ibuprofen, at any amount with a 2.4-fold higher likelihood of miscarriage compared with nonuse.
Seizure Risk
Convulsions and seizures can occur in ibuprofen overdose; seizures are reported rarely among severe overdose effects.
History & Culture
Ibuprofen emerged from research at Boots during the 1950s and 1960s that sought a safer alternative to aspirin.10 Stewart Adams and John Nicholson discovered it in 196111, and the team led by Adams synthesized the molecule and filed a patent…
Legality
By Country
Prescription1
CanadaPrescription onlyFood and Drugs Act, R.S.C. 1985, c. F-27, s. 29.1; Prescription Drug List: Human Use; Food and Drug Regulations, C.R.C., c. 870, ss. A.01.010 and C.01.0411920212223242526
Under the federal Prescription Drug List for human use, ibuprofen and its salts are prescription drugs, except in an oral dosage form providing 400 mg or less per dosage unit or a modified-release oral dosage form providing 600 mg or less per dosage unit. The listing took effect on 18 August 2016. The Food and Drug Regulations prohibit the sale of listed prescription drugs unless the seller has received a verbal or written prescription or the exception in section C.01.043 applies. The federal classification restricts sale and does not establish a general prohibition on ordinary possession; provinces and territories may further restrict the sale of products that are non-prescription federally.
Legal / decriminalized1
United StatesLegal (regulated)Federal Food, Drug, and Cosmetic Act § 503(b) (21 U.S.C. § 353(b)), FDA Drugs@FDA approval records for Motrin IB (NDA 019012) and ibuprofen tablets (ANDA 071268), and current DailyMed Structured Product Labels27282930231
In the United States, approved ibuprofen products are regulated under the Federal Food, Drug, and Cosmetic Act and FDA product approvals. FDA records classify Motrin IB 200 mg oral tablets under NDA 019012 as over-the-counter, while approved 400 mg, 600 mg, and 800 mg oral ibuprofen tablets under ANDA 071268 are prescription products. Under section 503(b) of the Federal Food, Drug, and Cosmetic Act, a drug limited by its approved application to use under professional supervision may be dispensed only by prescription. Marketing status depends on the product's application, strength, dosage form, and formulation.
References
Citations
Article Status
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