Salicylate metabolism: Effects of age and sex in adults

Montgomery, Patrick R.; Berger, Lisa; Mitenko, Paul A.; Sitar, Daniel S.

doi:10.1038/clpt.1986.98

Cited by 48 publications

(15 citation statements)

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“…Importantly, participants within that study were preselected for their likelihood to be compliant to long-term treatment, thus potentially conferring bias towards recruiting patients with lower risk of developing CVD events compared with the normal population, owing to differences in lifestyle choices. The potential for sex-based differences in salicylate metabolism may also account for the variability in the efficacy of aspirin between the sexes 30. Important caveats, therefore, need to be considered when considering the efficacy of aspirin in women when translating the findings from our population strategy to individual patients.…”

Section: Discussionmentioning

confidence: 99%

Age threshold for vascular prophylaxis by aspirin in patients without diabetes

Bulugahapitiya

Siyambalapitiya

Sithole

et al. 2008

Heart

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In the absence of significant bleeding risks, aspirin should routinely be considered for all men and women without diabetes above the ages of 48 and 57 years, respectively, for primary CVD prevention. For subjects below these age thresholds or for those above the age of 75 years, the decision to initiate aspirin should be based on a patient's individual cardiovascular risk profiles. These proposed age thresholds aim to take into account a patient's gender, bleeding risk and the cardioprotective benefits of low-dose aspirin treatment.

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Section: Discussionmentioning

confidence: 99%

Age threshold for vascular prophylaxis by aspirin in patients without diabetes

Bulugahapitiya

Siyambalapitiya

Sithole

et al. 2008

Heart

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“…Although gender-based differences in salicylate metabolism have been reported, 54 these do not appear to influence the pharmacodynamics of the antiplatelet effect of aspirin, which is substantially identical in men and women, both in terms of dose and time dependence. 2,55 A gender-related difference in the production of 15-epilipoxin A 4 has been reported in healthy subjects treated with low-dose aspirin (81 mg/d for 8 weeks).…”

Section: Is There a Gender-related Difference In The Cardioprotectivementioning

confidence: 99%

Aspirin: Promise and Resistance in the New Millennium

Patrono

Rocca

2008

ATVB

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Abstract-Although conceived at the end of the 19th century, aspirin remains the gold standard of antiplatelet therapy.Approximately 100 randomized clinical trials have established its efficacy and safety in the prevention of myocardial infarction, ischemic stroke, and vascular death among high-risk patients treated for a few weeks, at one end of the spectrum, and in low-risk subjects treated up to 10 years at the other. Despite this wealth of data, several issues continue to be debated concerning the use of aspirin as an antiplatelet agent, and novel opportunities appear on the horizon for this 110-year-old drug. These issues include: (1) the optimal dose for cardiovascular prophylaxis; (2) the uncertain threshold of cardiovascular risk for its use in primary prevention; (3) the apparent gender-related difference in its cardioprotective effects; (4) the increasingly popular theme of aspirin "resistance"; (5) the opportunities of chemoprevention in colorectal cancer; and (6) the renewed interest in aspirin as an analgesic agent in osteoarthritic patients at high cardiovascular risk. The aim of this review is to address these issues by integrating our current understanding of the molecular mechanism of action of the drug with the results of clinical trials and epidemiological studies of aspirin as an antiplatelet drug. A lthough conceived at the end of the 19th century, aspirin remains the gold standard of antiplatelet therapy. Approximately 100 randomized clinical trials have established its efficacy and safety in the prevention of myocardial infarction, ischemic stroke, and vascular death among highrisk patients treated for a few weeks, at one end of the spectrum, and in low-risk subjects treated up to 10 years at the other. 1,2 Despite this wealth of data, several issues continue to be debated concerning the use of aspirin as an antiplatelet agent, and novel opportunities appear on the horizon for this 110-year-old drug. These issues include: (1) the optimal dose for cardiovascular prophylaxis; (2) the uncertain threshold of cardiovascular risk for its use in primary prevention; (3) the apparent gender-related difference in its cardioprotective effects; (4) the increasingly popular theme of aspirin "resistance"; (5) the opportunities of chemoprevention in colorectal cancer; and (6) the renewed interest in aspirin as an analgesic agent in osteoarthritic patients at high cardiovascular risk.The aim of this review is to address these issues by integrating our current understanding of the molecular mechanism of action of the drug with the results of clinical trials and epidemiological studies of aspirin as an antiplatelet drug. The Optimal Dose of AspirinPlacebo-controlled randomized trials have shown that aspirin is an effective antithrombotic agent when used long term in doses ranging between 50 and 100 mg/d, and there is a suggestion that it is effective in doses as low as 30 mg/d. 2,3 Aspirin in a dose of 75 mg/d was shown to be effective in reducing the risk of acute myocardial infarction (MI) or death in pati...

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“…These reactions generally produce more water-soluble compounds that can then be excreted in urine (43). Some studies have suggested sexually dimorphic UDP-glucuronosyltransferase activity in humans and in mice, but results from other studies in humans have not supported these observations (49,50). A possible explanation for these conflicting results may be that, because multiple isoforms of UDP-glucuronosyltransferase enzymes exist (51,52), some may be affected by sex while others are not.…”

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confidence: 41%

Alteration in sexually dimorphic testosterone biotransformation profiles as a biomarker of chemically induced androgen disruption in mice.

Wilson

McLachlan

Falls

et al. 1999

Environ Health Perspect

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Assessment of the impact of environmental chemicals on androgen homeostasis in rodent models is confounded by high intraindividual and interindividual variability in circulating testosterone levels. Our goal was to evaluate changes in testosterone biotransformation processes as a measure of androgen homeostasis and as a biomarker of exposure to androgen-disrupting chemicals. Sexspecific differences in hepatic testosterone biotransformation enzyme activities were identified in CD-i mice. Gonadectomy followed by replacement of individual steroid hormones identified specific sex differences in biotransformation profiles that were due to the inductive or suppressive effects of testosterone. Notably, significant androgen-dependent differences in testosterone 6a-and 15a-hydroxylase activities were demonstrated, and the ratio of 6w and 15a-hydroxylase activities proved to be an excellent indicator of the androgen status within the animaL The male or "masculinized" testosterone 6alotISt-hydroxylase ratio was significantdy less than the female or "feminized" ratio. Male mice were exposed to both an antiandrogen, vinclozolin, and to a compound that modulates serum androgen levels, indole-3-carbinol, to test the utility of this ratio as a biomarker of androgen disruption. Treatment with the antiandrogen vinclozolin significantly increased the 6ax1l5a-hydroxylase ratio. Indole-3-carbinol treatment resulted in a dose-dependent, but highly variable, decrease in serum testosterone levels. The 6aIlSa-hydroxylase ratio increased as serum testosterone levels decreased in these animals. However, the increase in the ratio was much less variable and more sensitive than serum testosterone levels. These investigations demonstrate that the 6a/150-hydroxylase ratio is a powerfil measure of androgen modulation and a sensitive indicator of exposure to androgen-disrupting chemicals in CD-1 mice. Key work androgen disruption,.biomarker, biotransformation, sexually dimorphic metabolism, testosterone.

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Salicylate metabolism: Effects of age and sex in adults

Cited by 48 publications

References 0 publications

Age threshold for vascular prophylaxis by aspirin in patients without diabetes

Age threshold for vascular prophylaxis by aspirin in patients without diabetes

Aspirin: Promise and Resistance in the New Millennium

Alteration in sexually dimorphic testosterone biotransformation profiles as a biomarker of chemically induced androgen disruption in mice.

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