Ibuprofen - BioPharma Notes

Ibuprofen is first of the propionic acid derivative introduced in 1959 in United Kingdom. It is one of the most used NSAIDs and available as over the counter medicine.
It’s analgesic potency is like that of paracetamol. It is better tolerated and cost-effective among all propionic acid derivatives. Ibuprofen is available as generic medicine.

Indications of ibuprofen

It is useful in patients with osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. It is a good substitute for aspirin as an anti-inflammatory agent due to less side effects.
Used as analgesic. It can be used to treat mild to moderate pain like in primary dysmenorrhea, dental pain and headache.
Used as antipyretic agent.

Figure 1- Mechanism of action of NSAIDS including Ibuprofen

During pain, inflammation and fever, arachidonic acid is liberated from phospholipid fraction of cell membrane by phospholipase A2. Arachidonic acid is converted to prostaglandins (PGs) by cyclooxygenase (COX-1 and COX-2).
The prostaglandins produced sensitize blood vessels to other inflammatory mediators which increase permeability and sensitize chemical receptor of afferent pain ending to mediators such as histamine and bradykinin. PGE2 and PGI2 produce hyperalgesia associated with inflammation. They are also involved in pyretic response.
Ibuprofen is non-selective COX inhibitor. It inhibits COX enzymes and thus inhibit prostaglandin synthesis in brain resulting in its analgesic and anti-pyretic activity.

It is available as tablet or suspension. It is absorbed rapidly after oral administration and binds extensively to plasma proteins (90- 99%) and undergoes hepatic metabolism. Around 90% is metabolized to hydroxylate or carboxylate derivative.
Peak plasma concentration is attained in 1-2 hours of oral administration. Its plasma half-life is 1.8- 2 hours. It is eliminated in 24 hours after last dose and very little amount is excreted unchanged.
Its kinetics is not impaired in old age or renal impairment.

Around 5-15 % of patients experience GI related effects including gastric pain, vomiting, GI bleeding, increased risk of gastric ulcer.
Other side effects which are infrequent include thrombocytopenia, blurred vision, tinnitus, headache, dizziness, fluid retention, edema, interstitial nephritis and acute renal failure.
Patient who develop ocular disturbance should stop use of ibuprofen.

Drug Interactions are quite similar to other NSAIDs. The serious interaction may occur with warfarin, high dose methotrexate, anti-hypertensives, beta-blockers, diuretics and lithium. It increases the risk of bleeding with warfarin and increases the risk of bone marrow depression with high dose methotrexate. While using combination of ibuprofen and these drugs, anticipation and careful monitoring may be helpful to prevent serious events.
Ibuprofen also interfere with anti-platelet action of aspirin.

Contraindicated in:

Patients allergic or hypersensitive to ibuprofen, aspirin or any other NSAIDs/
Patients with increased risk of bleeding or with bleeding of stomach or intestine.
Heart attack or stroke.
In liver problems, stomach or intestinal ulcer.
Pregnancy.
Patients with history of gastric bypass surgery or in time immediately after coronary bypass surgery.

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Tan SC, Patel BK, Jackson SH, Swift CG, Hutt AJ. Ibuprofen stereochemistry: double-the-trouble? Enantiomer 1999;4(3-4):195-203.
Pharmacology and Pharmacotherapeutics book. 24th edition.
Goodman and Gillman’s Manual of Pharmacology and Therapeutics.
Lippincott Illustrated Reviews Pharmacology. 6th edition