Absorption and excretion of tolmetin in arthritic patients

Grindel, J M; Migdalof, Bruce H.; Plostnieks, Janis

doi:10.1002/cpt1979261122

Cited by 22 publications

(6 citation statements)

References 5 publications

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“…In unpublished work with individuals on long term tolmetin therapy suffering from rheumatoid synovitis of the knee, Desiraju et al (1982) found a tolmetin half-life of 6 hours in serum and 7.2 hours in synovial fluid. The observed serum half-life from these studies is substantially greater than that obtained in other reports of tolmetin pharmacokinetics (Cressman et al, 1976;Grindel et al, 1979).…”

Section: Tolmetincontrasting

confidence: 66%

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: Tolmetincontrasting

confidence: 66%

Antirheumatic Drug Concentrations in Human Synovial Fluid and Synovial Tissue

Wallis

Simkin²

1983

Clinical Pharmacokinetics

108

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“…On day 8, after a single 400-mg dose of tolmetin, blood and synovial fluid samples were obtained repeatedly for 24 hr. Blood (10 ml) were taken just prior to receiving the medication and then at 5, 15, 30, and 45 min and 1, 1.5, 2, 4, 6, 8,12,16,20, and 24 hr after the dose. The synovial fluid (2 ml) was sampled just prior to and 2, 8, 12, and 24 hr after the drug dose.…”

Section: Methodsmentioning

confidence: 99%

“…However, with only five data points, it is impossible to specifically model the synovial fluid kinetics of tolmetin. The average terminal synovial fluid t% of 6.9 + 2.3 hr was derived from only three points (8,12, 24 hr after the last dose). There were no significant differences between the terminal t %~ in plasma and synovial fluid (Student's paired t test).…”

Section: Patientmentioning

confidence: 99%

Tolmetin kinetics and synovial fluid prostaglandin E levels in rheumatoid arthritis

Dromgoole

Fürst

Desiraju

et al. 1982

Clin Pharmacol Ther

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Tolmetin kinetics were determined in the plasma and synovial fluid of five rheumatoid arthritis patients after they had ingested tolmetin (400 mg every 6 hr) for 7 days. Tolmetin was rapidly absorbed, with average peak levels in plasma and synovial fluid occurring at 45 min and 2 hr. The drug concentration in synovial fluid was higher than that in plasma for prolonged periods, while the rates of elimination from both plasma and synovial fluid were similar. The average half-lives of tolmetin in plasma and synovial fluid were 6.77 +/- 1.47 hr and 6.90 +/- 2.3 hr. Total prostaglandin E levels in synovial fluid of these patients were suppressed for at least 24 hr after the last dose of tolmetin, suggesting that PGE synthesis continues to be suppressed even by the very low concentrations of tolmetin remaining after 24 hr.

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“…Grindel et al (1979) found a significant increase in the renal clearance of tolmetin in arthritic patients. They concluded that a concomitant increase in Vd secondary to reported decreases in the plasma protein binding of tolmetin is the most likely explanation for the increased renal clearance of the drug.…”

Section: Tolmetinmentioning

confidence: 95%

Clinical Pharmacokinetics of Non-steroidal Anti-inflammatory Drugs

Verbeeck

Blackburn

Loewen

1983

Clinical Pharmacokinetics

214

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The number of non-steroidal anti-inflammatory drugs (NSAIDs) available for clinical use has dramatically increased during the last decade. As a general rule, NSAIDs are well absorbed from the gastrointestinal tract, with the exception of aspirin (and possibly diclofenac, tolfenamic acid and fenbufen) which undergoes presystemic hydrolysis to form salicylic acid. Concomitant administration of NSAIDs with food or antacids may in some cases lead to delayed or even reduced absorption. The NSAIDs are highly bound to plasma proteins (mainly albumin), which limits their body distribution to the extracellular spaces. Apparent volumes of distribution of NSAIDs are, therefore, very low and usually less than 0.2 L/kg. The elimination of these drugs depends largely on hepatic biotransformation; renal excretion of unchanged drugs is usually small (less than 5% of the dose). Total body clearance is low and for most NSAIDs is less than 200 ml/min. The effect of age and disease on the disposition of NSAIDs has not been extensively studied. Due to the central role of the liver in the overall elimination of the majority of these compounds, hepatic disease will most likely lead to a significant alteration in their pharmacokinetic behaviour. NSAIDs have been reported to be involved in numerous pharmacokinetic drug interactions. Aspirin decreases the plasma concentrations of many other NSAIDs, although the clinical significance of this is uncertain. Due to the extremely high plasma protein binding of NSAIDs (around 99% in many cases), competition for the same binding sites on plasma proteins may be at least partly responsible for some interactions of NSAIDs with other highly bound drugs; however, another mechanism such as decreased metabolism or decreased urinary elimination is usually involved as well. The most important interactions with NSAIDs are those involving the oral anticoagulants and oral hypoglycaemic agents, though not all NSAIDs have been found to interact with these drugs. In clinical practice, there appear to be no clear-cut guidelines to assist the clinician in the selection of the most appropriate drug for an individual patient. The selection of an anti-inflammatory drug should be based on clinical experience, patient convenience (e.g. once or twice daily dosage schedule), side effects and cost. Since a marked interindividual variability exists in the clinical response to a given NSAID, clinicians prescribing these agents may try several of them sequentially until an adequate response is obtained.

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Absorption and excretion of tolmetin in arthritic patients

Cited by 22 publications

References 5 publications

Antirheumatic Drug Concentrations in Human Synovial Fluid and Synovial Tissue

Antirheumatic Drug Concentrations in Human Synovial Fluid and Synovial Tissue

Tolmetin kinetics and synovial fluid prostaglandin E levels in rheumatoid arthritis

Clinical Pharmacokinetics of Non-steroidal Anti-inflammatory Drugs

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