Anti-inflammatory drugs pharmacokinetics

A few N-Mannich bases of the anti-inflammatory drug salicylamide are reported in Table 11.1. The pharmacokinetic behavior of one of these, N-(morpholinomethyl)salicylamide (11.54), was examined in the rabbit [90], Plasma concentration curves showed that the oral bioavailability of salicylamide was increased two- to sixfold by administration of the prodrug. 

Landoni, M.F. and Lees, P., Pharmacokinetic/pharmacodynamic modeling of non-steroidal anti-inflammatory drugs,/. Vet. Pharmacol. Ther., 20,118-120,1997. 

Lin, J.H., Cocchetto, D.M. and Duggan, D.E. (1987) Protein binding as a primary determinant of the clinical pharmacokinetic properties of non-steroidal anti-inflammatory drugs. Clinical Pharma-cokinetks, 12, 402-432. 

J.R.B.J. Brouwers, and P.A.G.M. de Smet, Pharmacokinetic-pharmacodynamic drug interactions with nonsteroidal anti-inflammatory drugs. Clin. Pharmacokinet. 27 462-485, 1994. 

Drug interactions with lithium have been reviewed (569-573) another review focused on interactions in the elderly (573). A review of drug interactions with lithium considered both pharmacokinetic interactions [for example diuretics, nonsteroidal anti-inflammatory drugs (NSAIDs)] and pharmacodynamic interactions (for example antipsychotic drugs, SSRIs) and summarized the most important ones in tabular form (569). 

The 2-arylpropionic acid ( profen ) non-steroidal anti-inflammatory drugs, each of which contains a single chiral center, are formulated as racemic (50 50) mixtures of the S(+)- and R(-)-enantiomers, with the exception of naproxen, which is formulated as the S(- -)-enantiomer. Based on inhibition of cyclooxygenase activity, the S(- -)-enantiomer is the eutomer (more potent enantiomer). These drugs differ markedly in both pharmacodynamic activity and pharmacokinetic behavior and, in addition, enantiomer pharmacokinetics of each drug varies among animal species. After intravenous administration of racemic keto-profen to horses, sheep, and 20-week-old calves and measurement of individual enantiomers in plasma, significant differences between the enantiomers were found in systemic clearance in horses and in both systemic clearance and volume of distribution in sheep... 

Hutt, A.J. Caldwell, J. The importance of stereochemistry in the clinical pharmacokinetics of the 2-arylpropionic acid non-steroidal anti-inflammatory drugs. Clin. Pharma-cokinet. 1984, 9, 371-373. 

The COX-2 selective non-steroidal anti-inflammatory drug celecoxib did not alter the pharmacokinetics or the hypoprothrombinemic effect of warfarin in 24 healthy subjects (30). However, there have been at least two reports of increased INR in patients taking stable warfarin therapy and celecoxib (31,101). 

Day RO, Graham GG, Williams KM. Pharmacokinetics of non-steroidal anti-inflammatory drugs. Bailliere s Clin Rheumatol 1988 2(2) 363-93. 

Evans, A.M. (1992) Enantioselective pharmacodynamics and pharmacokinetics of chiral non-steroidal anti-inflammatory drugs. European Journal of Clinical Pharmacology, 42, 237-256. 

Lees, P., McKellar, Q.A., May, S. Ludwig, B. (1994) Pharmacodynamics and pharmacokinetics of carprofen in the horse. Equine Veterinary Journal, 23, 203-208. McCormack, K. Brune, K. (1991) Dissociation between the antinociceptive and antiinflammatory effects of the nonsteroidal anti-inflammatory drugs a survey of their analgesic efficacy. Drugs, 41, 533-547. 

Even when the major metabolite is inactive, clinically important pharmacokinetic changes may occur in patients with renal failure. The non-steroidal anti-inflammatory drugs that derive from propionic acid (for... 

Stevens, A.J. Martin, S.W. Brennan, B.S. McLachlan, A. Gifford, L.A. Rowland, M. Houston, J.B. Regional drug delivery II Relationship between drug targeting index and pharmacokinetic parameters for three non-steroidal anti-inflammatory drugs using the rat air pouch model of inflammation. Pharm.Res., 1995, 12, 1987-1996... 

Probenecid but not cidofovir alters zidovudine pharmacokinetics such that zidovudine doses should be reduced when probenecid is present, as should the doses of drugs similarly affected by probenecid fe.g., /i-lactam antibiotics, nonsteroidal anti-inflammatory drugs [NSAIDs], acyclovir, lorazepam, furosemide, methotrexate, theophylline, and rifampin). Concurrent nephrotoxic agents are contraindicated, and an interval of 1 week before beginning cidofovir treatment is recommended after prior exposure to aminoglycosides, intravenous pentamidine, amphotericin foscamet, NSAIDs, or contrast dye. Cidofovir and oral ganciclovir in combination are poorly tolerated at full doses. 

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