Concentrations of ibuprofen in serum and synovial fluid from patients with arthritis [proceedings]

Glass, R. C.; Swannell, AJ

doi:10.1111/j.1365-2125.1978.tb04624.x

Cited by 31 publications

(11 citation statements)

References 6 publications

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“…Stereospecific disposition of ibuprofen enantiomers occurs into the synovial fluids of arthritic patients, many of whom have synovitis or inflammation of their knees. There is appreciable accumulation of R/S-ibuprofen in synovial fluids with broad peaks occurring over a period of 2-6 h which follows the peak plasma or serum concentrations (Glass and Swannell 1978;Mäkelä et al 1981;Albert and Gernaat 1984;Gallo et al 1986). The ratios of total ibuprofen concentrations in the synovial fluid to those in plasma is about 1.24 at 7 h following single dose of 600 mg of the drug and 0.52-1.46 at 3-12 h after 3 daily doses of ibuprofen 1.8 g day -1 (Gallo et al 1986).…”

Section: Pharmacokinetics In Adultsmentioning

confidence: 96%

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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Section: Pharmacokinetics In Adultsmentioning

confidence: 96%

Ibuprofen: pharmacology, efficacy and safety

2009

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“…Ibuprofen passes slowly into the synovial spaces and may remain there in high concentrations after the plasma concentrations have declined (Glass and Swannell, 1978;Whitlam et al, 1981). Ibuprofen is not excreted in measurable quantities in breast milk.…”

Section: Distributionmentioning

confidence: 97%

Clinical Pharmacokinetics of Non-steroidal Anti-inflammatory Drugs

Verbeeck

Blackburn

Loewen

1983

Clinical Pharmacokinetics

212

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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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“…Both of these findings may be related to the inability of plasma measurements to reflect drug concentrations at inflammatory sites in the tissues. It has been shown previously that synovial fluid ibuprofen levels lag behind plasma concentrations and stay elevated for longer (Glass & Swannell, 1978) although the unbound drug concentration in synovial fluid has recently been shown to be about equal to plasma unbound concentrations (Whitlam etal., 1981).…”

Section: N\omentioning

confidence: 99%

Dose‐response study with ibuprofen in rheumatoid arthritis: clinical and pharmacokinetic findings.

Grennan¹,

Aarons²,

Siddiqui³

et al. 1983

Brit J Clinical Pharma

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Clinical response and plasma pharmacokinetics were studied in 20 rheumatoid patients receiving three dosages of ibuprofen. There was a significant response to 1600 mg daily of ibuprofen by all three clinical measurements but increasing the daily dosage to 2400 mg produced no overall increase in response. The AUC increased with increasing daily drug dosages from 800 to 2400 mg daily and the dose normalised AUC fell by 15% over the same dosage range. The fraction of ibuprofen not bound to plasma proteins increased with increasing dosage and may contribute to the fall in the dose normalised AUC. There was a considerably inter‐individual variation in the AUC. There was no significant correlation between AUC and clinical response as measured by articular index and there was a weakly significant correlation between AUC and clinical response as measured by a visual analogue pain index. Pharmacokinetic variables probably account for only a small part of the inter‐individual variation in response of rheumatoid patients treated with increasing dosages of the non‐steroidal, anti‐inflammatory drug ibuprofen.

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Concentrations of ibuprofen in serum and synovial fluid from patients with arthritis [proceedings]

Cited by 31 publications

References 6 publications

Ibuprofen: pharmacology, efficacy and safety

Ibuprofen: pharmacology, efficacy and safety

Clinical Pharmacokinetics of Non-steroidal Anti-inflammatory Drugs

Dose‐response study with ibuprofen in rheumatoid arthritis: clinical and pharmacokinetic findings.

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