Simultaneous Pharmacokinetics Ofbenorylate Inplasma and Synovial Fluid of Patients with Rheumatoid Arthritis

Aylward, Mansel; Maddock, J.; Rees, P.; Thomas, G.; Wheeldon, R.; Holly, Frederick W.

doi:10.3109/03009747609095636

Cited by 9 publications

(3 citation statements)

References 6 publications

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“…Aylward et al (1976) have shown benorylate to peak later and lower in synovial fluid than in the plasma, with an equilibration time of approximately 75 minutes. Synovial fluid concentrations declined very slowly most probably because of slow release from articular fat stores.…”

Section: Benorylatementioning

confidence: 98%

Antirheumatic Drug Concentrations in Human Synovial Fluid and Synovial Tissue

Wallis

Simkin²

1983

Clinical Pharmacokinetics

108

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Antirheumatic drug concentrations have been measured in human synovial fluid and synovial tissue, and provide insights on: (1) extravascular pharmacokinetics; (2) articular pathophysiology; and (3) the factors which modify drug levels in inflamed tissues. Concentrations of free drug in synovial fluid and plasma are the same in all conditions except rheumatoid and infectious arthritis, where the most severely afflicted joints may contain lower synovial fluid drug concentrations. This finding may be relevant to the chronicity and intractability of chronic arthritis. After single-dose therapy and a characteristic 'equilibration time', higher concentrations are found in synovial fluid than in plasma - a phenomenon which results from relative drug sequestration across the trans-synovial diffusion barrier away from the organs of elimination. Studies of oral, parenteral, topical and intra-articular antirheumatic drug therapy are reviewed, and recommendations are made for the conduct of future studies.

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Section: Benorylatementioning

confidence: 98%

Antirheumatic Drug Concentrations in Human Synovial Fluid and Synovial Tissue

Wallis

Simkin²

1983

Clinical Pharmacokinetics

108

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“…However, in all cases where simultaneous plasma and SF drug concentrations have been measured, the concentrations in SF are lower than those in plasma (Sholkoff et al, 1967;Emori et al, 1973;Thomas et al, 1975;Aylward et al, 1976;Jalava et al, 1977;Farr & Willis, 1977;Glass & Swannell, 1978;Ray et al, 1979;Soren, 1979;Chiccarelli et al, 1980). The pharmacological effects of NSAID are generally considered to be related to the levels achieved in SF (Emori et al, 1973).…”

Section: Introductionmentioning

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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“…Benorilat daha sonra sinoviyal sıvıda birikmeye başlamış ve bu nedenle plazmada tayin edilememiştir. Bu farmakokinetik bulgular Benorilat'ın diğer antiinflamatuvar ilaçlara göre, etki yöresine daha çabuk ulaştığını ve daha fazla sinoviyal sıvıya geçtiğini kanıtlamaktadır (52,53 Farmakolojik aktivitenin değerlendirildiği çalışma sonuçları, Benorilat'ın bu açıdan da hedefe ulaştığını göstermekte ve aspirin'e hemen eşdeğer antiinflamatuar aktivite gösteren…”

Section: Benorilatın Kimyasal öZellikleriunclassified