Protein binding of non‐steroidal anti‐inflammatory drugs in plasma and synovial fluid of arthritic patients.

Wanwimolruk, Sompon; Brooks, Peter; Birkett, D. J.

doi:10.1111/j.1365-2125.1983.tb01469.x

Cited by 38 publications

(12 citation statements)

References 24 publications

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“…Moreover, it has often been shown that the protein concentration greatly affects the free fraction of drugs, since protein binding is reduced in diseases associated with hyp~albuminemia,~~,~'.~~ and is less in synovial fluid than in plasma, corresponding to the difference in protein concentrations between these media. 21, 32 In the case of our study, none of these explanations can be valid, since the number of molecule.of ligand bound per molecule of albumin increases with increasing albumin concentration except at 20 and 40 gfiter HSA, where the ketoprofen binding was proportional to the protein concentration. The results obtained at 20 and 40 ghter confirmed those obtained in a protein binding study of salicylate.…”

Section: Plasma Protein Binding Of Ketoprofenmentioning

confidence: 66%

Stereoselective protein binding of ketoprofen: Effect of albumin concentration and of the biological system

Dubois

Lapicque

Abiteboul³

et al. 1993

Chirality

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Equilibrium dialysis was used to study in vitro the enantioselective binding of R, S, and racemic ketoprofen at physiological pH and temperature in human serum albumin (HSA) (1, 20, and 40 g/liter) and in plasma. The binding of enantiomers in a racemic mixture was studied to see the effect of each isomer on the other's interaction with the protein. The free fractions were determined by high-performance liquid chromatography. The binding of ketoprofen enantiomers to albumin was enantioselective, depending on both drug and protein concentrations. Enantioselectivity was observed in plasma too but was the opposite of that in HSA at 40 g/liter. The percentage of each isomer unbound was higher in the racemic mixture than with the isomer alone. The displacement of probes specific for HSA sites I and II, studied by spectrofluorimetry, suggests that all three preparations of ketoprofen are bound mainly to site I and secondarily to site II.

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Section: Plasma Protein Binding Of Ketoprofenmentioning

confidence: 66%

Stereoselective protein binding of ketoprofen: Effect of albumin concentration and of the biological system

Dubois

Lapicque

Abiteboul³

et al. 1993

Chirality

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“…Thus, the protein binding is less in diseases associated with hypoalbuminaemia, such as rheumatoid arthritis (Netter et al 1984). In the same manner, the lower binding in synovial fluid compared with that in plasma was related to the difference in protein concentrations in these 2 liquids (Wanwimolruk et al 1983). Few data in the literature concerned the implications of various conditions on the stereoselective binding of NSAIDs.…”

Section: Discussionmentioning

confidence: 93%

Protein Binding and Stereoselectivity of Nonsteroidal Anti-Inflammatory Drugs

Lapicque¹,

Muller²,

Payan³

et al. 1993

Clinical Pharmacokinetics

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Stereoselective binding of nonsteroidal anti-inflammatory drugs (NSAIDs) can be studied using various techniques. Thus the results obtained by different investigators may be poorly consistent and even contradictory. NSAIDs are bound stereoselectively to serum albumin to different degrees depending on the drug investigated (ibuprofen, indoprofen, carprofen, etodolac, ketoprofen and flurbiprofen). For other drugs, both enantiomers are bound to a similar extent (pirprofen, fenoprofen). This stereoselectivity could vary with experimental conditions, in particular with protein concentration (ketoprofen, etodolac), leading to individual differences. Finally, the stereoselectivity of protein binding and of pharmacokinetics can be compared: differences in binding between enantiomers can explain their differences in pharmacokinetics, once metabolic properties such as inversion have been taken into account.

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“…The binding of ibuprofen in plasma compared with synovial fluids depends on the concentrations of albumin in these compartments (Wanwimolruk et al 1983). There are differences in the affinity of S(?)…”

Section: Pharmacokinetics In Adultsmentioning

confidence: 99%

Ibuprofen: pharmacology, efficacy and safety

2009

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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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Protein binding of non‐steroidal anti‐inflammatory drugs in plasma and synovial fluid of arthritic patients.

Cited by 38 publications

References 24 publications

Stereoselective protein binding of ketoprofen: Effect of albumin concentration and of the biological system

Stereoselective protein binding of ketoprofen: Effect of albumin concentration and of the biological system

Protein Binding and Stereoselectivity of Nonsteroidal Anti-Inflammatory Drugs

Ibuprofen: pharmacology, efficacy and safety

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