Drug metabolism ibuprofen

Bapuji AT, Rambhau D, Srinivasu P, Rao BR, Apte SS. Time dependent influence of diazepam on the pharmacokinetics of ibuprofen in man. Drug Metabol Drug Interact 1999 15(1) 71-81. 

Pettersen, J.E., Blessington, B. and Jellum, E. (1975), Ibuprofen metabolism studied by combined gas chromatography-mass spectrometry Dialysis fluid - a convenient medium for studies in drug metabolism. Scand. J. Clin. Lab. Invest., 35, Suppl. 143, 147 (Abstract). 

Fenoprofen (Nalfon) is chemically and pharmacologically similar to ibuprofen and is used in the treatment of rheumatoid arthritis, osteoarthritis, and mild to moderate pain. GI effects such as dyspepsia and pain are most common, although dizziness, pruritus, and palpitations may occur. GI bleeding, sometimes severe, has been reported, and interstitial nephritis has been rarely associated with this drug. Concomitant administration of aspirin decreases the biological half-Ufe of fenoprofen by increasing the metabolic clearance of hydroxy-lated fenoprofen. Chronic administration of pheno-barbital also decreases the drug s half-life. 

Ibuprofen, as shown in Scheme 11.8, affords an example of aliphatic hydroxylation. Other drugs similarly metabolized include terfenadine, pentobarbital, and cyclosporine. 

Various arylpropionic acids show similar specificity. For most, if not all, the (5) enantiomer is the pharmacologically active one, whereas the R) enantiomer is usually much less active, although the ratio of iS)/ R) activity varies from drug to drug (and species to species). Only one of these drugs, however, is administered as the separated (S) enantiomer (naproxen, Naprosyn ). Normally these drugs are considered safe, and one cannot readily differentiate between the relative activities of the (S) and (R) forms because the in vivo half-life is very short, typically one or two hours. In patients with impaired renal function, where clearance is much slower, however, problems can arise. From in vivo studies of ibuprofen, it was established that the (S)-(-l-) isomer was responsible for antiinflammatory activity. In vivo, however, the (/ )-(-) isomer may become active because there is stereoselective inversion from R) to (S) (but not from 5 to R) in vivo with a half-life of about two hours. This inversion apparently proceeds by stereoselective formation of the coenzyme A (CoA) ester of the (f )-(-)-arylpropionic acid, followed by epimerization and release of the (S)-(+)-enantiomer. This epimerization is observed in vivo before the oxidative metabolism. Such inversion from (R) to (S) in vivo is also known for fenoprofen and benoxa-profen, and is expected to occur for most of the drugs of this series. ... 

Vtric F, Haefeli WE, Drewe, J, et al. Interaction of ibuprofen and probenecid with metabolizing enzyme phenotyping procedures using caffeine as the probe drug. Br / Clin Pharmacol. 2003 55 191-198. 

Ibuprofen This is a commonly used nonsteroidal antiinflammatory drug. Side effects and overdose can results in gastrointestinal bleeding or a metabolic acidosis. 

Example Ibuprofen (Motrin, Advil, Nuprin) naproxen (Naprosyn) (Aleve is a similar OTC drug) Oxaprozin (Daypro) ketoprofen (Orudis). Route PO Pregnancy category B Pharmacokinetic Absorbed from the GI tract, metabolized in the liver and primarily excreted in urine ... 

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