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Ibuprofen: pharmacology, efficacy and safety

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Abstract

Objectives

This review attempts to bring together information from a large number of recent studies on the clinical uses, safety and pharmacological properties of ibuprofen. Ibuprofen is widely used in many countries for the relief of symptoms of pain, inflammation and fever. The evidence for modes of action of ibuprofen are considered in relation to its actions in controlling inflammation, pain and fever, as well as the adverse effects of the drug.

Summary of outcomes

At low doses (800–1,200 mg day−1) which in many countries are approved for non-prescription (over-the-counter) sale ibuprofen has a good safety profile comparable with paracetamol. Its analgesic activity is linked to its anti-inflammatory effects and is related to reduction in the ex vivo production in blood of cyclo-oxygenase (COX)-1 and COX-2 derived prostanoids. Higher prescription doses (circa 1,800–2,400 mg day−1) are employed long-term for the treatment of rheumatic and other more severe musculo-skeletal conditions. Recent evidence from large-scale clinical trials with the newer coxibs, where ibuprofen was as a comparator, have confirmed earlier studies which have shown that ibuprofen has comparable therapeutic benefits with coxibs and other NSAIDs. For long-term usage (6+ months) there are greater numbers of drop-outs due to reduced effectiveness of therapy, a feature which is common with NSAIDs. Spontaneous reports of adverse events and adverse drug reactions (ADRs) in clinical trails from long-term coxib comparator studies, as well as in epidemiological studies, shows that ibuprofen has relatively low risks for gastro-intestinal (GI), hepato-renal and other, rarer, ADRs compared with other NSAIDs and coxibs. A slightly higher risk of cardiovascular (CV) events has been reported in some, but not all studies, but the risks are in general lower than with some coxibs and diclofenac. The possibility that ibuprofen may interfere with the anti-platelet effects of aspirin, though arguably of low grade or significance, has given rise to caution on its use in patients that are at risk for CV conditions that take aspirin for preventing these conditions. Paediatric use of ibuprofen is reviewed and the main results are that the drug is relatively safe and effective as a treatment of acute pain and fever. It is probably more effective than paracetamol as an antipyretic.

Conclusions

This assessment of the safety and benefits of ibuprofen can be summarized thus: (1) Ibuprofen at OTC doses has low possibilities of serious GI events, and little prospect of developing renal and associated CV events. Ibuprofen OTC does not represent a risk for developing liver injury especially the irreversible liver damage observed with paracetamol and the occasional liver reactions from aspirin. (2) The pharmacokinetic properties of ibuprofen, especially the short plasma half-life of elimination, lack of development of pathologically related metabolites (e.g. covalent modification of liver proteins by the quinine–imine metabolite of paracetamol or irreversible acetylation of biomolecules by aspirin) are support for the view that these pharmacokinetic and notably metabolic effects of ibuprofen favour its low toxic potential. (3) The multiple actions of ibuprofen in controlling inflammation combine with moderate inhibition of COX-1 and COX-2 and low residence time of the drug in the body may account for the low GI, CV and renal risks from ibuprofen, especially at OTC doses.

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Abbreviations

ADME:

Absorption, distribution, metabolism and elimination

AEs:

Adverse events

AUC:

Area-under-the curve (plasma concentration)

CV:

Cardiovascular

CoA:

Coenzyme A

COX-1:

Cyclo-oxygenase-1

COX-2:

Cyclo-oxygenase-2

Coxibs:

COX-2 selective NSAIDs (a sub-group of NSAIDs)

Cl/F:

Clearance (fractional)

C max :

Maximal plasma concentration

CNS:

Central nervous system

Cp:

Plasma concentration

CYP:

Cytochrome P450

GI:

Gastrointestinal

K el :

Elimination rate

NOS:

Nitric oxide synthase (iNOS, inducible eNOS, endothelial, nNOS, neuronal)

NSAIDs:

Non-steroidal anti-inflammatory drugs

NS-NSAIDs:

Non-selective NSAIDs, i.e. those with approximately equivalent COX-1 and COX-2 inhibitory effects

OR:

Odds ratios

OTC:

Over-the-counter, non-prescription

PMNs:

Polymorphonuclear leucocyte

Rac-:

Racemic

tNSAIDs:

traditional NSAIDs, e.g. aspirin, ibuprofen, naproxen

t 1/2 :

Half-time of elimination

T max :

Time of maximal concentration

UDP:

Uridine diphosphate

V D :

Volume of distribution

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  1. Emeritus Professor of Biomedical Sciences, Biomedical Research Centre, Sheffield Hallam University, Howard Street, Sheffield, S1 1WB, UK

    K. D. Rainsford

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  1. K. D. Rainsford
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Rainsford, K.D. Ibuprofen: pharmacology, efficacy and safety. Inflammopharmacol 17, 275–342 (2009). https://doi.org/10.1007/s10787-009-0016-x

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