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Methods for in Vitro Skin Metabolism Studies
Published in Francis N. Marzulli, Howard I. Maibach, Dermatotoxicology Methods: The Laboratory Worker’s Vade Mecum, 2019
The metabolism of methyl salicylate was determined in viable and nonviable hairless guinea pig skin (Table 1). In viable skin over 50% of the absorbed compound was hydrolyzed to salicylic acid by esterases in skin. Twenty-one percent of the absorbed compound was further conjugated with glycine to form salicyluric acid. Greater esterase activity was observed in male skin. Esterase is a stable enzyme, and hydrolysis of methyl salicylate also occurred in nonviable skin. However, no conjugation of salicylic acid was observed in nonviable skin.
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Published in Caroline Ashley, Aileen Dunleavy, John Cunningham, The Renal Drug Handbook, 2018
Caroline Ashley, Aileen Dunleavy, John Cunningham
Salicylate is mainly eliminated by hepatic metabolism; the metabolites include salicyluric acid, salicyl phenolic glucuronide, salicylic acyl glucuronide, gentisic acid, and gentisuric acid. The formation of the major metabolites, salicyluric acid and salicyl phenolic glucuronide, is easily saturated and follows Michaelis-Menten kinetics. As a result, steady-state plasma-salicylate concentrations increase disproportionately with dose. Salicylate is also excreted unchanged in the urine; the amount excreted by this route increases with increasing dose and also depends on urinary pH, about 30% of a dose being excreted in alkaline urine compared with 2% of a dose in acidic urine. Renal excretion involves glomerular filtration, active renal tubular secretion, and passive tubular reabsorption.
Platelet response to aspirin in UK and Irish pregnancy cohorts: a genome-wide approach
Published in Platelets, 2022
Fionnuala Mone, Juhi K. Gupta, Marie M. Phelan, Shireen Meher, Lu Yung Lian, Ben Francis, Eunice Zhang, Cecilia Mulcahy, Ana Alfirevic, Fionnuala M. Mcauliffe, Kate Navaratnam
LDA’s short half-life and rapid clearance hinder detection and quantification of drug levels in maternal body fluids and are impractical for clinical research. Salicyluric acid (SUA) is the stable urinary metabolite of salicylic acid produced during LDA metabolism. Through a collaboration with experts in nuclear magnetic resonance (NMR), we developed an accurate, semi-automated method for detection of SUA in maternal urine samples of LDA-treated pregnant women. We demonstrated no specific sample preparation is required; SUA is stable at room temperature and through successive freeze-thaw cycles. SUA can readily and reproducibly be detected by NMR using ChenomxTM pattern recognition software (Chenomx, Canada) and expert review. This method has since been used for adherence assessment in clinical research [21]. In an attempt to determine patient acceptability with regards investigative methods of aspirin adherence testing, we assessed the findings from an anonymous questionnaire at 20–22 weeks’ gestation from the low-risk Dublin cohort.18
Metabolism of bioconjugate therapeutics: why, when, and how?
Published in Drug Metabolism Reviews, 2020
Hanlan Liu, Jayaprakasam Bolleddula, Andrew Nichols, Lei Tang, Zhiyang Zhao, Chandra Prakash
Subsequent in vivo metabolic profiles and characterization studies of edasalonexent in human plasma, mouse plasma/tissues, and dog plasma/tissues were generally consistent with the in vitro metabolic profiles (Liu et al. 2017). In dog, DHA was identified as one of the major metabolites in skeletal muscle and heart tissues whereas both Phase I (oxidation and amide hydrolysis) and Phase II (mainly glucuro-conjugation) metabolism were observed in plasma. In humans, the four major metabolites identified in human plasma were M1 and M2 (hydroxylation and/or epoxidation on DHA moiety), M10 (glucuronidation of M1 or M2), and M14 (glucuronidation). Three polar metabolites (salicyluric acid, SA, and SA-linker) were also detected in human plasma using hydrophilic interaction chromatography, which is an alternative approach to conventional reverse-phase chromatography for metabolite separation. Besides metabolite profiling, released bioactives and linkers associated with those bioactives were quantitated in vivo in nonclinical species and humans.
Is placing a victim in the left lateral decubitus position an effective first aid intervention for acute oral poisoning? A systematic review
Published in Clinical Toxicology, 2019
Vere Borra, Bert Avau, Peter De Paepe, Philippe Vandekerckhove, Emmy De Buck
One study investigated the effect of a left lateral position compared to remaining ambulant on the pharmacokinetics of crystalline sodium salicylate. It was shown that remaining ambulatory resulted in a statistically significant decrease of cumulative urinary excretion of salicyluric acid after 2 h and 4 h [35].