Ibuprofen is rapidly absorbed after oral administration, reaching peak concentration within 15-30 minutes and have a high affinity for plasma proteins, with 99% of the drug attached to these. The AUC is dose dependent. At higher dosages of 600 mg, there is an increase in the free fraction, leading to increased clearance, also dose dependent.

This NSAID slowly passes into the synovial spaces of which also fades slowly, maintaining higher concentrations than in the blood for longer. The elimination half-life is about two hours, with rapid and complete removal. Over 90% of the ingested dose is excreted in the urine as metabolites or conjugated derivatives. Ibuprofen is excreted in very modest quantities in breast milk.

The pharmacokinetics of ibuprofen is influenced minimally by the elderly, alcoholic liver disease or chronic inflñamatorias musculoskeletal diseases.

The bioavailability of the drug in tablets is not essentially different from the effervescent granules, nor is different behavior between young adults and elderly patients.

Taking ibuprofen together with other anti-inflammatory substances produces a sum of risks of adverse effects without significant potentiation of the analgesic or anti-inflammatory. Concurrent use produces inhibition of platelet function, which increases the risk of bleeding.

For this reasonit is not advisable to take simultaneously both types of medicine. Of this recommendation are excluded the small doses of aspirin prescribed for cardiovascular prophylaxis, although ibuprofen can interfere with the antiplatelet effect of low-dose aspirin. On the balance of probabilities for interference of ibuprofen with aspirin is more likely to interact than not, being more likely in patients who are chronic ibuprofen takers and most important in high cardiovascular risk patients. It is therefore reasonable to prevent the latter cases chronic consumption of ibuprofen.

There have been studies that indicate that taking ibuprofen decreases the rate of antiplatelet effect of aspirin taken later. It is believed that the interaction is caused by blockage of ibuprofen to platelet cyclooxygenase. Mean inhibition of thromboxane B2 by 80 mg of aspirin is 98.0% (95% CI: 96.8-99.2%). This proportion decreases sharply by the concurrent administration of ibuprofen to 86.6% (95% CI: 77.6-95.1%).

It is also postulated that the basic mechanism of the interaction between the ibuprofen and salicylates resides in the displacement of these binding proteins. After being displaced aspirin protein binding, this drug undergoes an increased removal, decreasing its plasma concentration, although the unbound fraction of salicylate blood remains stable.

It has been published a case of thrombosis of the aneurysm while was in regression phase in a patient with Kawasaki disease. This complication was attributed to blocking caused by ibuprofen while the patient were taking aspirin. This illustrates the importance of avoiding the use of ibuprofen when using aspirin as antiplatelet agent. In these patients, if Ibuprofen is unavoidable , should be taken two hours after aspirin.

The concomitant intake of alcohol and ibuprofen alters more visual and auditory memory than alcohol alone, as evidenced by studies in healthy volunteers.

Some observations indicate that ibuprofen and other substances can reduce the effect of alcohol on behavior or cognitive ability, but these effects have not been found in similar studies by other researchers.

Although the antacids do not affect the extent of absorption of ibuprofen, the concurrent intake of those influences the speed with which this antiinflammatory is absorbed.

Available data indicate that antacids may increase or decrease the rate and the beginning of ibuprofen absorption specifically for each antacid. Thus, the magnesium hydroxide increases the solubility, dissolution rate and bioavailability, while the aluminum hydroxide has a retarding effect.

According to some data, concurrent and prolonged use of magnesium hydroxide and ibuprofen can lead to irritation and gastric mucosal changes, so should be avoided concomitant and prolonged use of both drugs .

In short-term studies, are not recorded substantial effects on prothrombin time in patients treated with oral anticoagulants. However, ibuprofen can cause gastrointestinal bleeding, inhibition of platelet aggregation and prolonged bleeding time and there are several observations of gastrointestinal bleeding with simultaneous administration of both substances. Must proceed with extreme caution while concomitantly.

In almost half of the patients in a cohort of elderly treated with acenocoumarol, INR increased beyond the therapeutic rangewith an increase of this value between 1 and 4.

Ibuprofen can cause significant clinical problems in some patients receiving chronic anticoagulation, especially in elderly patients taking multiple medications. Some experts recommend controlling bleeding time a few days after starting treatment with ibuprofen, suspending his administration if it reaches values ??above the normal range.

Concurrent use increases the risk of gastrointestinal bleeding and ulcers.

Ibuprofen may increase the hypoglycaemic effect of sulfonylureas. However, some studies show that administration of antiinflammatory drug counteracts the effect of tolbutamide.

Ibuprofen reduces the antihypertensive effect of ACE inhibitors, increasing the risk of renal failure and elevates blood potassium (hyperkalemia). Ibuprofen has an opposite effect on tubular excretion of water and sodium that ACE , which is particularly relevant in patients who require increased water and sodium excretion, as hypertensive disease and heart failure.

The mechanism of action is related to the inhibition of prostaglandins synthesis that causes inflamatory and vasodilators effects, which increase renal blood flow and promote the excretion of sodium and water.

Patients taking ACE inhibitors and ibuprofen together, should be closely monitored (kidney function, blood pressure), inasmuch as may occur accused effects of rise in blood pressure, which usually starts after five days from the beginning of the simultaneous intake.

Both voriconazole as fluconazole increase to double exposure to S-ibuprofen, likely due to inhibition of CYP2C9. It is advisable assess the possibility of reducing the dosage of ibuprofen when administered at the same time that these imidazole derivatives.

Coadministration of cyclosporin and NSAIDs increases cyclosporin nephrotoxicity due to antiinflammatory effects on renal prostaglandins.

It is recommended Administering ibuprofen at lowest dose possible.

Compared with controls, patients receiving cimetidine recorded peak ibuprofen concentration higher (64 vs 56 mcg / ml). There was no difference in the removal of ibuprofen compared to controls. The impact of cimetidine is of little clinical importance.

This substance alters the stereoselective disposition of ibuprofen in healthy volunteers, increasing the formation of R-ibuprofenoil-coenzyme A, rather than by an effect on the oxidative metabolism of ibuprofen. In some cases this interaction potential therapeutic implications.

This substance reduces the rate and extent of absorption of ibuprofen, with a possible decrease in the effect of this. Cholestyramine significantly reduced AUC (26%, p <0.05) and Cmax (34.4%, p <0.01), with increased Tmax (80%, p <0.01).

It is advisable to administer the antiinflammatory two hours before or six after cholestyramine.

As in the case of other anti-inflammatory drugs, taking jointly ibuprofen and corticosteroids increases the risk of bleeding and gastrointestinal ulcers, especially in elderly.

Concurrent use increases digoxin levels after one week of treatment, according to a study. The average increase of the digoxinemia was 59% (95% CI 10.7-325.4, P <.05).

The ibuprofen may decrease the diuretic and antihypertensive effect of these substances. It may be advisable to increase the dose of diuretic.

Patients with impaired renal function taking potassium-sparing diuretics and suffer a worsening of that, may be at risk of suffering a potentially fatal rise in serum potassium.

Oral ibuprofen increases the AUC of furosemide in 36-37%, decreasing the clearance of the diuretic, but has limited clinical relevance.

It is estimated that the daily administration of 1800 mg of ibuprofen induces a significant increase in systolic blood pressure in elderly patients treated with thiazide.

Gemfibrozil increases moderately AUC and prolongs the half-life of R-ibuprofen, possibly through the CYP2C8. No clinical significance..

Are mentioned in the literature some cases of interaction per concurrent use of this plant and ibuprofen.

The joint use can cause an increase in the concentration of lithium and a reduction of its elimination, although there are important differences between individuals.

Has been published the case of a 60-years woman treated with lithium that showed a marked increase in the levels of antipsychotic (4.2 mmol/l), with subsequent renal failure while was taking 1600 mg of ibuprofen a day.

From this and other cases it appears that patients who take anti-inflammatory with lithium should be monitored every 4-5 days the level of this substance and the dosage adjusted if necessary. It is also recommended to reduce the dose of lithium when beginning treatment with ibuprofen.

Ibuprofen administration very close to that of methotrexate (less than 24 hours before) can result in elevated levels of this substance, with the risk of toxicity.

Pretreatment with naltrexone does not diminish the peak analgesic of ibuprofen, but prolonged duration of action (mechanism not established).

Has been reported a case of aseptic meningitis, irreversible sensorineural hearing loss and vestibulopathy by concurrent use of ranitidine, ciprofloxacin and ibuprofen.

The mechanism invoked by the authors of the observation is a hypersensitivity reaction that would affect the meninges and, in part, to the cochlea.

Coadministration of tacrolimus and NSAIDs increases its nephrotoxicity, due to NSAIDs effects on renal prostaglandin.

An study on healthy volunteers concludes that the tamarind (Tamarindus indica) significantly increases the bioavailability of ibuprofen (mechanism not established).

Ibuprofen during pregnancy

Ibuprofen during lactation

Ibuprofen : Patient information

Brands of Ibuprofen in major markets

Date of update of this page: November 10, 2008.