Ibuprofen (2-(4-isobutylphenyl)propionic acid, C₁₃H₁₈O₂) is a chiral propionic acid NSAID with a stereogenic α-carbon. The (S)-(+) enantiomer is pharmacologically active (COX inhibitor); the (R)-(−) enantiomer is inactive but is converted to the S form in vivo by α-methylacyl-CoA racemase. Commercial ibuprofen is the racemic mixture.
Reversible competitive COX inhibition
Unlike aspirin, ibuprofen occupies the COX active site channel through non-covalent interactions (Van der Waals, hydrophobic contacts with Phe-381, Leu-384, Tyr-385). When plasma ibuprofen falls, the enzyme is free and recovers activity.
Critical clinical consequence: Platelet inhibition by ibuprofen is temporary — function recovers ~24 h after the last dose. This contrasts sharply with aspirin's irreversible 8–10 day platelet inhibition. A pharmacodynamic interaction: ibuprofen taken before aspirin competes for the same COX-1 site, blocking aspirin's access and preventing its irreversible acetylation — potentially nullifying aspirin's cardioprotective effect in patients on low-dose aspirin therapy.
Renal risk: hidden prostaglandins
In normal conditions, renal prostaglandins (PGE₂, PGI₂, mainly COX-2) play a minor role in blood flow regulation. Under hemodynamic stress — dehydration, heart failure, diuretic use, cirrhosis — they become critical for maintaining afferent arteriole vasodilation and glomerular filtration. Ibuprofen in these situations can precipitate acute renal failure. Risk is especially high in patients >65, with CKD, diabetes, or heart failure, and in dehydrated states (gastroenteritis, intense heat exercise).