Biotransformation of Salicylic Acid to Its Acyl and Phenolic Glucuronides in Man

Tsuchiya, Tamehiro; Levy, Gerhard

doi:10.1002/jps.2600610530

Cited by 35 publications

(5 citation statements)

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“…It may account for more than 70% of a dose of SA in the low-dose range (3)(4)(5). Schachter and Manis (6) have reported that the renal clearance of SU in man does not exceed the approximate renal plasma flow and that the salicylurate-to-inulin renal clearance ratio observed after administration of salicylate agreed with the clearance data previously determined by others after administration of salicylurate.…”

Section: Introductionsupporting

confidence: 80%

“…It should be clearly understood that the pharmacokinetic "constants" obtained in the manner described here only describe the time course of salicylate concentrations in the range studied, and do not apply to concentrations above or below this range. The metabolic fate of salicylate is quantitatively very dependent upon dose and urine pH (5). In normal subjects, 66% of the dose used in this study will, on the average, be converted to salicyluric acid and less than 5% will be excreted in unmetabolized form (5).…”

Section: Discussionmentioning

confidence: 99%

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Kinetics of Salicylate Elimination by Anephric Patients

Löwenthal¹,

Briggs²,

Levy³

1974

J. Clin. Invest.

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A B S T R A C T The objectives of this research were to determine the kinetics of salicylate elimination in anephric patients and particularly to establish if these patients form the major metabolite of salicylic acid, salicyluric acid, at a normal rate. This investigation was initiated because of conflicting reports concerning the contribution of the kidneys to the formation of salicyluric acid in man. Six patients, 20-44 yr old, three of whom were anatomically anephric while the other three were physiologically anephric, received an intravenous injection of 500 mg salicylic acid (as sodium salicylate)/1.73 m' body surface area on an interdialysis day. Serial blood samples were obtained for 12 or 16 h after injection and the plasma was assayed for salicylic acid, salicyluric acid, total protein, albumin, and creatinine. Detailed pharmacokinetic analysis based on an open, two-compartment linear model revealed no significant differences in apparent volume of distribution and apparent first-order distribution and elimination rate constants between the anephric patients and normal adult subjects. An estimate of salicyluric acid formation rate by the anephric patients, based on the initial rate of increase of salicylurate concentrations in plasma, indicates that the metabolite is formed at a normal rate. These results suggest that the kidneys do not contribute significantly to the formation of salicyluric acid from salicylic acid in man. INTRODUCTIONThe elimination of salicylic acid (SA)1 in man involves urinary excretion of the unmetabolized drug and formation of salicyluric acid (SU), salicyl phenolic glucuronide, salicyl acyl glucuronide, and gentisic acid. A

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Section: Introductionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Kinetics of Salicylate Elimination by Anephric Patients

Löwenthal¹,

Briggs²,

Levy³

1974

J. Clin. Invest.

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“…It is therefore possible that in vitro, salicylic acid inhibits the formation of an interme diate metabolite without being converted to salicyluric acid. The lack of in vitro forma tion of salicyluric acid is difficult to explain since, in vivo, salicyluric acid is the major metabolite of salicylic acid [6,20],…”

Section: Discussionmentioning

confidence: 99%

Conjugation of Benzoic Acid with Glycine in the Human Fetal and Adult Liver and Kidney

Pacifici¹,

Mogavero²,

Giuliani³

et al. 1991

Dev Pharmacol Ther

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The rate of hippuric acid formation was measured in the homogenates obtained from 26 specimens of human adult liver, 9 specimens of human mid-gestational fetal liver, 5 specimens of human adult kidney and 11 specimens of human mid-gestational fetal kidney. The average (pmol/min/mg tissue ± SD) rate of hippuric acid formation was 322 ± 99 (adult liver), 7.6 ± 3.6 (fetal liver), 284 ± 117 (adult kidney) and 6.4 ± 6.7 (fetal kidney). One third of the fetal livers and kidneys studied were inactive in the formation of hippuric acid. These findings indicate that the conjugation of carboxylic acid with glycine is poorly developed in the mid-gestational human fetus. The kinetics of the formation of hippuric acid were studied in 3 fetal and adult livers and also in 3 fetal kidneys and in 3 specimens of the cortex and medulla of adult kidneys. The transformation of the data into Eadie-Hofstee plots generated straight lines in fetal and adult livers and kidneys. The Michaelis-Menten constant for the formation of hippuric acid (mean ± SD, mM) was 43.4 ± 6.6 (adult liver), 27.3 ± 10.1 (fetal liver), 33.3 ± 6.1 (adult renal cortex), 34.7 ± 11.3 (adult renal medulla) and 15.3 ± 3.5 (fetal kidney). The maximum velocity of the reaction (mean ± SD, pmol/min/mg tissue) was 204 ± 47.8 (adult liver), 6.0 ±1.3 (fetal liver), 199 ± 40.7 (adult renal cortex), 24.2 ± 16.9 (adult renal medulla) and 6.4 ± 1.8 (fetal kidney). The inhibitory effect of 8 drugs containing a carboxylic acid group on the rate of hippuric acid formation was studied in 3 adult livers. Salicylic acid and diflunisal were the most powerful as inhibitors. Ibuprofen, furosemide and sodium valproate were weak inhibitors, whereas ketoprofen, naproxen and captopril did not inhibit the formation of hippuric acid. The IC(50) values (mean ± SD) of salicylic acid and diflunisal on the rate of hippuric acid formation were 0.19 ± 0.05 and 1.18 ± 0.19 mM, respectively.

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“…18 SA is then either renally excreted or fi rst converted to one of four known derivatives (salicyl acyl glucuronide, gentisic acid, salicyl phenolic glucuronide, or salicyluric acid) before subsequent renal excretion. 19,20 The rates of absorption of ASA and SA from the stomach, the rates of conversion from one compound to another, and the rates of excretion of the various ASA derivatives are shown in Figure 4, which were all identifi ed from the relevant literature. 18,[21][22][23] The constants and modeling formulas, such as those indicated for ASA, were used to automatically produce the concentration data for the compounds in various compartments over time, resulting in a time series for each compound and each compartment affected.…”

Section: The Datamentioning

confidence: 99%

Spatiotemporal integration of molecular and anatomical data in virtual reality using semantic mapping

Soh

Turinsky

Trinh

et al. 2009

IJN

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Abstract:We have developed a computational framework for spatiotemporal integration of molecular and anatomical datasets in a virtual reality environment. Using two case studies involving gene expression data and pharmacokinetic data, respectively, we demonstrate how existing knowledge bases for molecular data can be semantically mapped onto a standardized anatomical context of human body. Our data mapping methodology uses ontological representations of heterogeneous biomedical datasets and an ontology reasoner to create complex semantic descriptions of biomedical processes. This framework provides a means to systematically combine an increasing amount of biomedical imaging and numerical data into spatiotemporally coherent graphical representations. Our work enables medical researchers with different expertise to simulate complex phenomena visually and to develop insights through the use of shared data, thus paving the way for pathological inference, developmental pattern discovery and biomedical hypothesis testing.

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Biotransformation of Salicylic Acid to Its Acyl and Phenolic Glucuronides in Man

Cited by 35 publications

References 5 publications

Kinetics of Salicylate Elimination by Anephric Patients

Kinetics of Salicylate Elimination by Anephric Patients

Conjugation of Benzoic Acid with Glycine in the Human Fetal and Adult Liver and Kidney

Spatiotemporal integration of molecular and anatomical data in virtual reality using semantic mapping

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