In-vitro and in-vivo metabolism of different aspirin formulations studied by a validated liquid chromatography tandem mass spectrometry method

Dei, Michele; Rizzo, Jessica; Scavone, Mariangela; Femia, Eti Alessandra; Podda, Gian Marco; Bossi, Elena; Bignotto, Monica; Caberlon, Sabrina; Cattaneo, Marco; Paroni, Rita

doi:10.1038/s41598-021-89671-w

Cited by 10 publications

(7 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Note that the xenobiotics cluster in CSF was signi cantly predictive of DCI status, and much of this predictive power was driven by higher CSF salicylate in DCI + patients. Plasma salicylate likely arose from aspirin intake and its subsequent deacetylation [29], which would be higher in DCI + patients and may well represent a surrogate marker of frequency of headache at aSAH onset. It could be important to monitor aspirin intake and the underlying reasons for aspirin use in aSAH patients.…”

Section: Discussionmentioning

confidence: 99%

Identification of a predictive multiplex biomarker of delayed cerebral ischemia and early metabolic deregulation after aneurysmal subarachnoid haemorrhage based on metabolomics and lipidomics

Chikh

Tonon

Triglia

et al. 2023

Preprint

View full text Add to dashboard Cite

BACKGROUND. Delayed cerebral ischaemia (DCI) following aneurysmal subarachnoid haemorrhage (aSAH) is a major cause of complications and death. Here we set out to identify high-performance predictive biomarkers of DCI and its underlying metabolic disruptions using metabolomics and lipidomics approaches. METHODS. This single-centre retrospective observational study enrolled 61 consecutive patients with severe aSAH requiring external ventricular drainage between 2013 and 2016, among them 22 experienced a DCI. Blood and cerebrospinal fluid (CSF) were sampled within the first 24 h after admission. We carried out LC-MS/MS-based plasma and CSF metabolomic and lipidomic profiling together with total fatty acids analysis. RESULTS. We identified a panel of 20 metabolites that together showed high predictive performance for DCI (area under the receiver operating characteristic curve: 0.968). This panel of metabolites included lactate, cotinine, salicylate, 6 phosphatidylcholines, and 4 sphingomyelins. Early biological disruptions that might explain the subsequent DCI found systemic hypoxia driven mainly by higher blood lactate, arginine and proline metabolism likely associated to vascular NO, dysregulation of the citric acid cycle in the brain, defective systemic energy metabolism and disrupted ceramide/sphingolipid metabolism. We also unexpectedly found a potential influence of gut microbiota on the onset of DCI. CONCLUSION. We identified a predictive metabolomic/lipidomic signature of further DCI in aSAH patients at admission to a NeuroCritical Care Unit. This signature is associated with significant systemic and cerebral biological dysregulations and reveal a potential link between DCI and gut microbiota. We conclude that targeting early peripheral hypoxia could help in preventing DCI. Clinical trial registration Clinicaltrials.gov identifier: NCT02397759

show abstract

Section: Discussionmentioning

confidence: 99%

Identification of a predictive multiplex biomarker of delayed cerebral ischemia and early metabolic deregulation after aneurysmal subarachnoid haemorrhage based on metabolomics and lipidomics

Chikh

Tonon

Triglia

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Note that the xenobiotic cluster in CSF was significantly predictive of further DCI status, and much of this predictive power was driven by higher CSF salicylate concentrations in DCI+ patients. Plasma salicylate likely arose from aspirin intake and its subsequent deacetylation, which would be higher in DCI + patients and may well represent a surrogate marker of the frequency of headache at aSAH onset. It could be important to monitor aspirin intake and the underlying reasons for aspirin use in adolescent aSAH patients.…”

Section: Discussionmentioning

confidence: 99%

Early Metabolic Disruption and Predictive Biomarkers of Delayed-Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage

Chikh,

Tonon,

Triglia

et al. 2023

J. Proteome Res.

View full text Add to dashboard Cite

Delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) is a major cause of complications and death. Here, we set out to identify high-performance predictive biomarkers of DCI and its underlying metabolic disruptions using metabolomics and lipidomics approaches. This single-center prospective observational study enrolled 61 consecutive patients with severe aSAH; among them, 22 experienced a DCI. Nine patients without aSAH were included as validation controls. Blood and cerebrospinal fluid (CSF) were sampled within the first 24 h after admission. We identified a panel of 20 metabolites that, together, showed high predictive performance for DCI. This panel of metabolites included lactate, cotinine, salicylate, 6 phosphatidylcholines, and 4 sphingomyelins. The interplay of the metabolome and the lipidome found between CSF and plasma in our patients underscores that aSAH and its associated DCI complications can extend beyond cerebral implications, with a peripheral dimension as well. As an illustration, early biological disruptions that might explain the subsequent DCI found systemic hypoxia driven mainly by higher blood lactate, arginine, and proline metabolism likely associated with vascular NO and disrupted ceramide/sphingolipid metabolism. We conclude that targeting early peripheral hypoxia preceding DCI could provide an interesting strategy for the prevention of vascular dysfunction.

show abstract

“…Полученные фармакокинетические параметры существенно не отличаются от данных, опубликованных ранее в литературе [11,16,18].…”

Section: результаты и обсуждениеunclassified

Analysis of Pharmacokinetic Parameters of Acetylsalicylic Acid for Prediction of Potential Nephrotoxic Effects

Красных¹,

Goroshko²,

Василенко³

et al. 2021

Bezopasnost' i risk farmakoterapii

View full text Add to dashboard Cite

Nonsteroidal anti-inflammatory drugs, including acetylsalicylic acid, can have a dose-dependent nephrotoxic effect. The study of the pharmacokinetics of acetylsalicylic acid products will contribute to timely detection and correction of side effects caused by this medicinal product.The aim of the study was to evaluate potential nephrotoxic effects following a single oral administration of 75 mg of acetylsalicylic acid, based on the analysis of the pharmacokinetic parameters.Materials and methods: the study involved 24 healthy volunteers who received 75 mg of acetylsalicylic acid (tablets) once orally. The measurement of the active metabolite of acetylsalicylic acid—salicylic acid—in blood plasma was performed by HPLC/MS using an Agilent 1200 liquid chromatography system coupled to an Agilent 6140 tandem mass spectrometer. Agilent Eclipse XDB-C18 column (4.6 mm×150 mm; 5.0 μm) was used for chromatographic separation. The test procedure used in the study was validated. The results obtained were used to calculate the pharmacokinetic parameters: Cmax (maximum concentration), Tmax (time to maximum concentration), T1/2 (half-life of the drug), AUC0-t (area under the pharmacokinetic curve from 0 to the last time point of the curve), AUC0-∞ (total area under the pharmacokinetic curve from 0 to ∞), MRT (mean residence time of the drug in the blood), Kel (elimination rate constant), Cl/F (total clearance), Vd/F (apparent volume of distribution). The Statistics (22.0.0.0) software was used for statistical processing of the results.Results: T1/2 of salicylic acid in blood plasma was determined to be 1.6 ± 0.5 h, Cmax was 4523.0 ± 725.0 ng/mL, and Tmax was 0.98 ± 0.4 h. AUC0–t was equal to 16183.0 ± 3823.0 ng×h/m, Vd/F was 12.0 ± 3.1 L/kg, and MRT was 2.9 ± 0.6 h.Conclusions: the analysis of the pharmacokinetic parameters demonstrated a high absorption rate, intensive distribution, and moderate elimination rate of salicylic acid (the main metabolite of acetylsalicylic acid), indicating a low risk of nephrotoxic effects associated with the studied dose of the drug.

show abstract

In-vitro and in-vivo metabolism of different aspirin formulations studied by a validated liquid chromatography tandem mass spectrometry method

Cited by 10 publications

References 35 publications

Identification of a predictive multiplex biomarker of delayed cerebral ischemia and early metabolic deregulation after aneurysmal subarachnoid haemorrhage based on metabolomics and lipidomics

Identification of a predictive multiplex biomarker of delayed cerebral ischemia and early metabolic deregulation after aneurysmal subarachnoid haemorrhage based on metabolomics and lipidomics

Early Metabolic Disruption and Predictive Biomarkers of Delayed-Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage

Analysis of Pharmacokinetic Parameters of Acetylsalicylic Acid for Prediction of Potential Nephrotoxic Effects

Contact Info

Product

Resources

About