Pharmacokinetics of aspirin and salicylate in elderly subjects and in patients with alcoholic liver disease

Roberts, Michael S.; Rumble, Roger; Wanwimolruk, Sompon; Thomas, Dylan C.; Brooks, Peter

doi:10.1007/bf00543800

Cited by 78 publications

(29 citation statements)

References 25 publications

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“…Due to their versatile use, ready availability over the counter and frequent use among the elderly, the pharmacokinetics of the salicylates in the elderly have been evaluated in a number of studies (Castleden et al, 1977;Salem & Stevenson, 1977;Cuny et al, 1979;Roberts et al, 1983). Castleden et al (1977), Cuny et al (1979) and Roberts et al (1983) have shown that most of the pharmacokinetic parameters were not significantly different between young and elderly patients, even though a marked increase in elimination half-life (Cuny et al, 1979) and apparent volume of distribution (Cuny etal., 1979;Roberts etal., 1983) was noted in the elderly group. However, no differences were noted in the area under the curve (AUC) of plasma salicylate concentration in these two age groups.…”

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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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: 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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“…Many of the previous single dose studies of salicylate pharmacokinetics in healthy volunteers used a dose equivalent of greater than 1,200 mg of aspirin (Bochner et al, 1981;Day et al, 1988;Netter et al, 1984;Roberts et al, 1983). These studies required at least a 12 h period of frequent blood sampling and more than 24 h of urine collection.…”

Section: Discussionmentioning

confidence: 99%

“…study were similar to that found in other single dose aspirin studies (900 mg to 1,500 mg) with respect to AUC(SA), AUCu(SA), the apparent volume of distribution (V), peak SA plasma concentration (Cmax), time to peak (tmax) and SA clearance (CL(SA) etc. (Cham et al, 1980;Graham et al, 1977;Gunsberg et at., 1984;Roberts et al, 1983). Minor differences between the data sets can be attributed to variation in the mg kg71 dose, the age, sex and/or health status of the subjects involved in the various studies.…”

Section: Discussionmentioning

confidence: 99%

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Salicylate pharmacokinetics in patients with rheumatoid arthritis.

Roberts

Friesen

et al. 1989

Brit J Clinical Pharma

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1 The pharmacokinetics of salicyclic acid (SA) and its major metabolite salicyluric acid (SU) were studied in nine patients with rheumatoid arthritis following a 900 mg oral dose of acetylsalicylic acid and during 6 weeks of chronic administration of enteric coated aspirin (3,900 mg day). Response to therapy was also monitored. 2 The various pharmacokinetic parameters determined in the study were similar to those observed in other single dose salicylate studies amongst healthy volunteers but were not predictive of salicylate concentration in the chronic dose study. 3 Plasma concentrations of SA (total and unbound) were found to decline significantly over the 6 weeks and plasma SU concentrations increased. 4 During the chronic dosing study, there was a significant increase in the Vmax (total and unbound) for the formation of SU, whilst the Km and SU clearance remained constant. Also, the elimination rate constant (k) for salicylate was not significantly affected. 5 Therapeutic response to salicylate therapy was not significantly affected by the decline in SA concentrations.

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“…Depending on the dose administered, Sal has a half-life of between 2 and 15 h or more (Furst et al, 1979;Roberts et al, 1983). The present study used sodium salicylate (NaSal) because of its longer half-life and to eliminate the anticoagulant effect from the acetate moiety of aspirin.…”

Section: Introductionmentioning

confidence: 99%

Vasoconstriction Caused by Cocaine is Enhanced by Sodium Salicylate: Is Inducible Nitric Oxide Synthase mRNA Related?

Mendoza-Baumgart

Pravetoni

Sparber

2004

Neuropsychopharmacol

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We have previously found that sodium salicylate (NaSal), injected into chicken eggs at nontoxic doses used for quantifying hydroxyl free radicals in hearts and brains of embryos, caused or exacerbated hemorrhages and dramatically reduced hatchability when combined with cocaine (Coc). It has also been reported that inducible nitric oxide synthase (iNOS) gene expression is altered in brain in response to vascular damage and inflammation. In this study we measured diameters of membrane-bound blood vessels (BV) before and after pretreatment with saline (NaCl) or NaSal (100 mg/kg egg), followed by infusion of either NaCl or Coc HCl (total of 67.5 mg/kg egg) during 15 min. Brains and hearts of the embryos were then analyzed for iNOS messenger RNA (mRNA) concentrations. Coc caused vasoconstriction that was significant 5 min postinfusion (5 min PI) of the entire dose (ie after 67.5 mg/kg egg). Significant vasoconstriction was evident within 5 min in the group injected with NaSal followed by infusion with Coc (ie after 22.5 mg Coc/kg egg). Expression of iNOS mRNA was significantly increased only in the brains of the group exposed to NaSal plus Coc, and the increase was inversely related to BV diameter. These data are discussed in relation to effects of salicylate upon prostanoid synthesis and/or nitric oxide synthesis via iNOS inhibition and their possible relationship to Coc-associated cerebral vascular and/or cardiovascular events in abusing humans.

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Pharmacokinetics of aspirin and salicylate in elderly subjects and in patients with alcoholic liver disease

Cited by 78 publications

References 25 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.

Salicylate pharmacokinetics in patients with rheumatoid arthritis.

Vasoconstriction Caused by Cocaine is Enhanced by Sodium Salicylate: Is Inducible Nitric Oxide Synthase mRNA Related?

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