Plasma and synovial fluid kinetics of flurbiprofen in rheumatoid arthritis.

Aarons, Leon; Salisbury, R; Alam-Siddiqi, M; Taylor, L; Grennan, D M

doi:10.1111/j.1365-2125.1986.tb05170.x

Cited by 21 publications

(13 citation statements)

References 22 publications

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“…Separate identification of these processes was not possible without plasma data. A similar model has been used to describe the synovial profile of flurbiprofen in patients with rheumatoid arthritis (Aarons et al, 1986). Following dosing with naproxen sodium, the entry of naproxen into the synovial fluid was rapid and its elimination was slow.…”

Section: Resultsmentioning

confidence: 99%

“…On this basis, a once-daily dosage regimen would appear adequate to maintain the therapeutic effect. Although relevant estimations of synovial halflife are lacking in the literature, there is a tendency to find a delayed elimination of NSAIDs from the synovial fluid relative to plasma (Wallis & Simkin, 1983;Aarons et al, 1986;McCrea et al, 1986;Netter et al, 1987).…”

Section: Resultsmentioning

confidence: 99%

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Naproxen kinetics in synovial fluid of patients with osteoarthritis.

Bruno¹,

Iliadis²,

Jullien³

et al. 1988

Brit J Clinical Pharma

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1. The kinetics of naproxen in synovial fluid were studied in 407 osteoarthritic outpatients with knee effusion requiring aspiration, following a single 1100 mg oral dose of naproxen sodium. 2. The drug concentration‐time profiles were described by a biexponential function. Naproxen entered synovial fluid rapidly, reaching a maximum concentration of 36 mg l‐1 (Cmax) at 7.5 h. The first order input rate constant (kOs) was 0.41 +/‐ 0.15 h‐1 with a lag time (tlag) of 0.24 +/‐ 0.36 h. 3. Elimination from the fluid was slow (t1/2 = 31 +/‐ 12 h) and appreciable drug concentrations were still measurable (27 mg l‐1) after 24 h. 4. During once daily dosing of naproxen sodium, naproxen should accumulate in synovial fluid, a steady‐state being achieved within a week of treatment. The predicted accumulation ratio based on trough concentration was 2.4.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Naproxen kinetics in synovial fluid of patients with osteoarthritis.

Bruno¹,

Iliadis²,

Jullien³

et al. 1988

Brit J Clinical Pharma

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“…It is likely that free drug approaches diffusional equilibrium across the synovium. Thus, at steady-state the free concentrations of salicylates (Rosenthal et al 1964), ibuprofen (Whitlam et al 1981), isoxicam (Bannwarth et al 1986) and flurbiprofen (Aarons et al 1986) equilibrate on both sides of the synovial membrane. Although in inflammatory joint diseases the albumin-bound fraction diffuses better across the membrane, because of the increased capillary permeability to proteins, the total NSAID concentrations at steady-state are lower in synovial fluid than those concurrently in plasma.…”

Section: Pharmacological Factorsmentioning

confidence: 96%

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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“…These individuals were included in a previous study of 29 patients in whom the plasma and synovial fluid concentrations of racemic flurbiprofen had been measured along with thermographic measurements (Aarons et al, 1986 Chromatography was carried out using a Spherisorb 150 x 4.6mm 3 pLm silica column with u.v. detection (245 nm) at a flow rate of 0.8 ml min-'.…”

Section: Methodsmentioning

confidence: 99%