Pharmacokinetics and Metabolic Rates of Acetyl Salicylic Acid and Its Metabolites in an Otomi Ethnic Group of Mexico

Lares‐Asseff, Ismael; Juárez-Olguı́n, Hugo; Flores‐Pérez, Janett; Guillé-Pérez, A; Vargas, Arturo

doi:10.1248/bpb.27.706

Cited by 11 publications

(4 citation statements)

References 19 publications

(12 reference statements)

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“…Williams et al [30] reported significantly lower plasma esterase activity (hydrolysis of ASA to SA) in individuals from Ghana compared to individuals living in the UK. Another group observed significant differences in SUA and several other pharmacokinetic parameters between two ethnic groups in Mexico [4]. Finally, in a twin study, Furst et al [29] reported that variations in excretion rates of SA and SUA were significantly smaller between identical twins than between fraternal twins, suggesting genetic influences in metabolism.…”

Section: Discussionmentioning

confidence: 99%

“…High interindividual variation in aspirin (ASA) metabolism and therapeutic response has been observed and is attributed to many factors, including concomitant use of other drugs or alcohol [1], urinary pH [2], sex [3], ethnicity [4], and variants in metabolizing enzymes involved in glucuronidation of ASA metabolites [i.e., UDP-glucuronosyltransferases (UGT)] [5,6]. The present analysis extends previous work to include an evaluation of the influence of dietary factors on ASA metabolism.…”

Section: Introductionmentioning

confidence: 99%

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Determinants of Aspirin Metabolism in Healthy Men and Women: Effects of Dietary Inducers of UDP-Glucuronosyltransferases

et al. 2011

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Background/Aims: Interindividual variation in aspirin (ASA) metabolism is attributed to concomitant use of drugs or alcohol, urine pH, ethnicity, sex, and genetic variants in UDP-glucuronosyltransferases (UGT). Little is known about the effects of diet. Methods: We evaluated cross-sectionally whether urinary excretion of ASA and its metabolites [salicylic acid (SA), salicyluric acid (SUA) phenolic glucuronide (SUAPG), salicylic acid acyl glucuronide (SAAG) and salicylic acid phenolic glucuronide (SAPG)] differed by UGT1A6 genotype and dietary factors shown to induce UGT. Following oral treatment with 650 mg ASA, urine was collected over 8 h in 264 men and 264 women (21–45 years old). Results: There were statistically significant differences in metabolites excreted between sexes and ethnicities. Men excreted more SUA; women more ASA (p = 0.03), SA, SAAG and SAPG (p ≤ 0.001 for all). Compared to Caucasians, Asians excreted more ASA, SA and SAAG, and less SUA and SUAPG (p ≤ 0.03 for all); African-Americans excreted more SAAG and SAPG and less SUA (p ≤ 0.04). There was no effect of UGT1A6 genotypes. Increased ASA and decreased SUAPG excretion was observed with increased servings of vegetables (p = 0.008), specifically crucifers (p = 0.05). Conclusion: Diet may influence the pharmacokinetics of ASA, but effects may be through modulation of glycine conjugation rather than glucuronidation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Determinants of Aspirin Metabolism in Healthy Men and Women: Effects of Dietary Inducers of UDP-Glucuronosyltransferases

et al. 2011

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“…It appears that hydrolysis of both drugs takes place in the gastrointestinal track and/or the liver because the hydrolytic metabolites, immediately following oral administration, are the predominant forms in the systemic circulation (Kees et al, 1996;Heestermans et al, 2006). In addition, the overall hydrolysis of both drugs exhibits a large interindividual variation (Slugg et al, 2000;Lares-Asseff et al, 2004), suggesting that the enzyme(s) for the hydrolysis is expressed differentially depending on individuals or there are polymorphic variants for this enzyme.…”

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confidence: 99%

Antiplatelet Agents Aspirin and Clopidogrel Are Hydrolyzed by Distinct Carboxylesterases, and Clopidogrel Is Transesterificated in the Presence of Ethyl Alcohol

Tang

Mukundan²,

Yang³

et al. 2006

J Pharmacol Exp Ther

226

183

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Aspirin (acetylsalicylic acid) and clopidogrel are two major antithrombogenic agents that are widely used for the treatment and prevention of cerebro-and cardiovascular conditions such as stroke. Combined use produces enhanced therapeutic effect. Aspirin and clopidogrel both are esters, and hydrolysis leads to decreased or inactivated therapeutic activity. The aim of the study was to determine whether aspirin and clopidogrel are hydrolyzed by the same enzyme(s), thus reciprocally prolonging the antithrombogenic activity. To test this possibility, microsomes from the liver and intestine were assayed for the hydrolysis of aspirin and clopidogrel. In contrary to the hypothesis, aspirin and clopidogrel were hydrolyzed in a tissue-differential manner. Liver microsomes hydrolyzed both drugs, whereas intestinal microsomes hydrolyzed aspirin only. Consistent with the tissue distribution of two carboxylesterases human carboxylesterase (HCE) 1 and HCE2, recombinant HCE1 hydrolyzed clopidogrel, whereas recombinant HCE2 hydrolyzed aspirin. In addition, hydrolysis of clopidogrel among liver samples was correlated well with the level of HCE1, and hydrolysis of aspirin with HCE2. Certain natural variants differed from the wild-type enzymes on the hydrolysis of aspirin or clopidogrel. In the presence of ethyl alcohol, clopidogrel is converted to ethyl clopidogrel. Carboxylesterases are important pharmacological determinants for drugs containing ester linkages and exhibit a large interindividual variation. The isoform-specific hydrolysis of aspirin and clopidogrel suggests that these two antithrombogenic agents may have pharmacokinetic interactions with different sets of ester drugs, and the altered hydrolysis by polymorphic mutants provides a molecular explanation to the interindividual variation.

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“…The pharmacokinetics of ASA vary depending on the dose administered, age, race, and other internal and external factors [11][12][13][14][15][16]. A previous study reported that GA was associated with the toxic effects caused by the administration of ASA [17].…”

Section: Discussionmentioning

confidence: 99%

Novel absorbance peak of gentisic acid following the oxidation reaction

Hosokawa¹,

Shukuya²,

Sogabe³

et al. 2020

PLoS ONE

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Gentisic acid (GA), a metabolite of acetylsalicylic acid (ASA), and homogentisic acid (HGA), which is excreted at high levels in alkaptonuria, are divalent phenolic acids with very similar structures. Urine containing HGA is dark brown in color due to its oxidation. We recently reported a new oxidation method of HGA involving the addition of sodium hydroxide (NaOH) with sodium hypochlorite pentahydrate (NaOCl�5H 2 O), which is a strong oxidant. In the present study, we attempted to oxidize GA, which has a similar structure to HGA, using our method. We herein observed color changes in GA solution and analyzed the absorption spectra of GA after the addition of NaOH with NaOCl�5H 2 O. We also examined the oxidation reaction of GA using a liquid chromatography time-of-flight mass spectrometer (LC/TOF-MS). The results obtained indicated that GA solution had a unique absorption spectrum with a peak at approximately 500 nm through an oxidation reaction following the addition of NaOH with NaOCl�5H 2 O. This spectrophotometric method enables GA to be detected in sample solutions without expensive analytical instruments or a complex method.

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Pharmacokinetics and Metabolic Rates of Acetyl Salicylic Acid and Its Metabolites in an Otomi Ethnic Group of Mexico

Cited by 11 publications

References 19 publications

Determinants of Aspirin Metabolism in Healthy Men and Women: Effects of Dietary Inducers of UDP-Glucuronosyltransferases

Determinants of Aspirin Metabolism in Healthy Men and Women: Effects of Dietary Inducers of UDP-Glucuronosyltransferases

Antiplatelet Agents Aspirin and Clopidogrel Are Hydrolyzed by Distinct Carboxylesterases, and Clopidogrel Is Transesterificated in the Presence of Ethyl Alcohol

Novel absorbance peak of gentisic acid following the oxidation reaction

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