Binding of piroxicam to synovial fluid and plasma proteins in patients with rheumatoid arthritis

Trnavská, Z; Trnavskỳ, K; Zlnay, D

doi:10.1007/bf00542141

Cited by 15 publications

(12 citation statements)

References 17 publications

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“…In (Rosenthal et al, 1964;Soren, 1979;Trnavska & Trnavsky, 1980) and ibuprofen (Whitlam et al, 1981) in SF than in the corresponding plasma. It has been suggested that the lower total drug concentrations in SF than in plasma is due to lower protein binding in SF.…”

Section: Resultsmentioning

confidence: 99%

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

Wanwimolruk

Brooks

Birkett³

1983

Brit J Clinical Pharma

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1 The protein binding of seven non‐steroidal anti‐inflammatory drugs (indomethacin, tolmetin, salicylic acid, ibuprofen, flurbiprofen, naproxen and GP53,633) and warfarin was investigated by equilibrium dialysis in simultaneous samples of synovial fluid and plasma from 12 arthritic patients. 2 The protein binding of all drugs studied except warfarin and flurbiprofen was significantly lower in synovial fluid than in plasma. 3 The decreased protein binding of these drugs is likely to explain the lower total drug concentrations found in synovial fluid in comparison to plasma. 4 The lower albumin concentration plays an important role in determination of reduced drug binding in synovial fluid compared to plasma and the fatty acid concentration in synovial fluid may also influence the protein binding of some of these drugs.

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Section: Resultsmentioning

confidence: 99%

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

Wanwimolruk

Brooks

Birkett³

1983

Brit J Clinical Pharma

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“…Since only the free drug is available to diffuse across the endothelium and other biological barriers and to produce pharmacological effect at the receptor sites in extra vas- Rosen (1970) Abbreviations: P = human plasma; A = human serum albumin; S = human serum; ED = equilibrium dialysis; FP = fluorescence probe; UF = ultrafiltration; NA = not available. Ayres et al (1977); Brogden et al (1981); Rogers et al (1981); Verbeeck et al (1983); Windholz (1983); Trnavska et al (1984); Physician's Desk Reference (1986) cular tissues as has been demonstrated explicitly for sulphonamides (Anton 1960) and other antibiotics (Kunin et al 1959(Kunin et al , 1973, phenytoin (diphenylhydantoin) [Booker & Darcey 1973;, warfarin propranolol (McDevitt et al 1976), it is more informative to express the protein binding of highly bound drugs such as NSAIDs in terms of their unbound fraction. For example, while a decrease in fraction bound from 0.99 to 0.98 may appear trivial at first sight, closer investigation shows this change represents a doubling of free fraction from 0.01 to 0.02 which may be clinically important.…”

Section: Basic Conceptsmentioning

confidence: 95%

Protein Binding as a Primary Determinant of the Clinical Pharmacokinetic Properties of Non-Steroidal Anti-Inflammatory Drugs

Lin

Cocchetto

Duggan

1987

Clinical Pharmacokinetics

188

101

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The ability of a wide variety of anionic, cationic, and neutral drugs to bind in a reversible manner to plasma proteins has long been recognised. Non-steroidal anti-inflammatory drugs (NSAIDs) are distinguished as a class by the high degree to which they bind to plasma protein. Plasma protein binding properties are primary determinants of the pharmacokinetic properties of the NSAIDs. Theoretical relationships are reviewed in order to define quantitatively the impact of plasma protein binding on clearance, half-life, apparent volume of distribution, and the duration and intensity of pharmacological effect. The quantitative relationships governing competitive displacement binding interactions are also presented. Experimental methods for in vitro and in vivo determination of the degree of plasma protein binding are discussed. The more common in vitro methods are equilibrium dialysis and ultrafiltration. Methods for characterising the degree of plasma protein binding in vivo consist of either measuring the concentration of drug at equilibrium in an implanted semipermeable vessel or measuring the relative drug concentrations in two body spaces with different protein content. Emphasis is given to the comparative advantages and disadvantages of experimental application of the various in vitro and in vivo methods. Plasma protein binding is discussed as a determinant of the trans-synovial transport of NSAIDs. Trans-synovial transport of NSAIDs appears to be a diffusional process. Limited data in humans receiving ibuprofen, indomethacin, aspirin, carprofen, alclofenac, or diclofenac suggest that clearance of each of these NSAIDs from the synovium is slower than clearance from plasma. The clinical data relevant to the relationship between plasma NSAID concentration and various measures of anti-inflammatory effect are reviewed. A positive correlation between plasma NSAID concentration and anti-inflammatory effect has been observed in only one study on naproxen and one study on piroxicam. In several other studies, the lack of concentration-response correlations is generally attributed to the relatively subjective, quantitatively inexact methods used to assess anti-inflammatory effect and analgesia in arthritic patients, as well as the substantial interpatient variabilities in the fraction of unbound NSAID and the unbound plasma NSAID concentration. In view of the generally poor correlation between concentration and therapeutic response, routine therapeutic monitoring of total plasma NSAID concentration is not recommended as a means of titrating individual dosages to the desired effect in each patient.(ABSTRACT TRUNCATED AT 400 WORDS)

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“…The binding of piroxicam to proteins in plasma and synovial fluid was studied by Trnavska et al (1984). The binding parameters (association constants and numbers of binding sites) in the 2 fluids were similar at a given (adjusted) albumin concentration from a given patient.…”

Section: Piroxicammentioning

confidence: 99%

Recent Findings on the Pharmacokinetics of Non-Steroidal Anti-Inflammatory Drugs in Synovial Fluid

Netter

Bannwarth

Royer-Morrot

1989

Clinical Pharmacokinetics

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Synovial fluid concentration is considered to be an important determinant of clinical response to non-steroidal anti-inflammatory drugs (NSAIDs). Trans-synovial transport of these drugs is a process of limited diffusion, governed partly by the pharmacological characteristics of NSAIDs and partly by the properties of the joint and joint space themselves. The studies which report simultaneous pharmacokinetics of NSAIDs in both plasma and synovial fluid compartments are of 2 types: (1) some compare the concurrent concentrations of drugs in plasma and joint fluid after a single administration. These provide pharmacokinetic information: (2) others, which conform more closely to the therapeutic conditions, look at synovial fluid and plasma concentrations after repeated administration of the drug. Recent findings on the pharmacokinetics of NSAIDs in synovial fluid are reviewed. These studies reveal 2 types of NSAIDs, according to their pharmacokinetic behaviour. First, there are NSAIDs with a short or intermediate plasma elimination half-life. These drugs equilibrate rapidly relative to their elimination; their peak synovial fluid concentrations occur later and are lower than those in plasma. Several hours after administration there is crossover of the concentration curves, and beyond this point, concentrations in synovial fluid may exceed those in plasma. During prolonged treatment, the synovial fluid concentrations of these NSAIDs fluctuate to a much lesser extent than plasma concentrations. Secondly, there are NSAIDs with a long plasma elimination half-life; their peak concentration in synovial fluid is also lower and later than that in plasma. At steady-state their concentrations (total and free) in synovial fluid are about half those in plasma. Numerous variables must be taken into account in attempts to correlate synovial fluid NSAIDs concentrations with clinical response, including protein binding and determination of both active metabolites and (eventually) the enantiomers.

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Binding of piroxicam to synovial fluid and plasma proteins in patients with rheumatoid arthritis

Cited by 15 publications

References 17 publications

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

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

Protein Binding as a Primary Determinant of the Clinical Pharmacokinetic Properties of Non-Steroidal Anti-Inflammatory Drugs

Recent Findings on the Pharmacokinetics of Non-Steroidal Anti-Inflammatory Drugs in Synovial Fluid

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