Increased Serum Salicylate Metabolites with Age in Patients Receiving Chronic Acetylsalicylic Acid Therapy

Montgomery, Patrick R.; Sitar, Daniel S.

doi:10.1159/000212493

Cited by 25 publications

(10 citation statements)

References 7 publications

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“…On the other hand, salicyluric acid plasma concentrations appeared to be significantly higher in the elderly than in the young subjects, which is in good agreement with the results of Montgomery & Sitar (1981). Similar to the finding of a recent study (Gunsberg et al, 1984), a correlation was found between the renal clearance of salicyluric acid and creatinine clearance.…”

Section: Discussionsupporting

confidence: 90%

“…In contrast, Salem & Stevenson (1977) found that the AUC of salicylate for elderly subjects was approximately twice that for young subjects. Recently, Montgomery & Sitar (1981) found higher steady-state plasma levels of salicyluric acid, a major metabolite of salicylate, in elderly patients receiving chronic ASA therapy. In addition, the metabolism of salicylate appears to be influenced by genetic factors (Furst et al, 1977), and plasma concentrations of ASA and salicylate have been found to be consistently higher in female than in male subjects (Coppe et al, 1981; Kelton et al, 1981;Buchanan et al, 1983).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The effects of age and sex on the disposition of acetylsalicylic acid and its metabolites.

Ho¹,

Triggs²,

Bourne³

et al. 1985

Brit J Clinical Pharma

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The disposition of a low dose (600 mg) of acetylsalicylic acid (ASA) and its metabolites (salicylate, salicyluric acid and salicyl glucuronides) was studied in 25 male and female patients of different ages. Plasma levels of ASA and salicylate were found to be significantly higher in the females (young and elderly), whereas plasma levels of salicyluric acid were found to be significantly higher in the elderly (male and female) groups. The higher plasma levels of ASA and salicylate in the females appear to be due to an intrinsically lower metabolic activity in that sex, while the lower clearance of salicyluric acid leads to the accumulation of that compound in the aged. No age and sex effects were found to influence the volumes of distribution of ASA, salicylate and salicyluric acid.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

The effects of age and sex on the disposition of acetylsalicylic acid and its metabolites.

Ho¹,

Triggs²,

Bourne³

et al. 1985

Brit J Clinical Pharma

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“…Recently, it has been reported that plasma concentrations of gentisic and salicyluric acids are significantly increased in patients over 60 years of age (Montgomery and Sitar, 1981). Further studies are obviously indicat~d to elucidate the possible correlation between altered disposition of salicylate and the propensity of geriatric patients to salicylism.…”

Section: Salicylatementioning

confidence: 98%

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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“…Salicylic acid in plasma was measured by the h.p.l.c. method of Montgomery & Sitar (1981 For in vivo studies, pooled plasma from a different panel of normal volunteers was used to study the effects of salicylic acid (100 mg/l) on plasma protein binding of isoxicam 5 to 20 mg/l added in vitro. For ex vivo studies, plasma obtained from the 10 volunteers in the isoxicam-ASA kinetic study was used.…”

Section: Introduction Methodsmentioning

confidence: 99%

Interaction of isoxicam with acetylsalicylic acid.

Esquivel¹,

Cussenot²,

East³

et al. 1984

Brit J Clinical Pharma

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Ten healthy male volunteers were given 200 mg p.o. of isoxicam after an overnight fast and the plasma concentrations over time followed for 96 h by h.p.l.c. Five days later enteric coated acetylsalicylic acid (ASA) 650 mg four times daily was started and continued for 10 days producing steady state trough plasma salicylate of 83 mg/l (range 21‐133). A second 200 mg isoxicam dose was given 5 days after starting ASA and the plasma concentration time‐curve again followed. After ASA, there was no change in lag time (0.54 vs 0.51 h), time to peak concentration (10 vs 10 h), or disappearance t1/2 (28.7 vs 31.0 h) however the peak isoxicam concentration and AUC were reduced 18 and 22% respectively (P less than 0.01). Plasma protein binding of isoxicam studied by equilibrium dialysis was 96 +/‐ 1% in the absence and 86 +/‐ 5% in the presence of ASA. The reduction in binding was unrelated to plasma SA concentrations achieved or observed reductions in AUC for plasma isoxicam. ASA decreased plasma isoxicam binding, peak plasma isoxicam concentrations and AUC without altering the apparent disappearance half‐life of total plasma isoxicam after a single oral dose.

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Increased Serum Salicylate Metabolites with Age in Patients Receiving Chronic Acetylsalicylic Acid Therapy

Cited by 25 publications

References 7 publications

The effects of age and sex on the disposition of acetylsalicylic acid and its metabolites.

The effects of age and sex on the disposition of acetylsalicylic acid and its metabolites.

Clinical Pharmacokinetics of Non-steroidal Anti-inflammatory Drugs

Interaction of isoxicam with acetylsalicylic acid.

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