Serum Predose Metabolic Profiling for Prediction of Rosuvastatin Pharmacokinetic Parameters in Healthy Volunteers

Rosuvastatin is a well-known lipid-lowering agent generally used for hypercholesterolemia treatment and coronary artery disease prevention. There is a substantial inter-individual variability in the absorption of statins usually caused by genetic polymorphisms leading to a variation in the correspon...

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Autores principales:	Anne Michelli Reis Silveira, Gustavo Henrique Bueno Duarte, Anna Maria Alves de Piloto Fernandes, Pedro Henrique Dias Garcia, Nelson Rogerio Vieira, Marcia Aparecida Antonio, Patricia de Oliveira Carvalho
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	personalized medicine metabolomics rosuvastatin prediction machine learning pharmacometabolomics Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/ee722c3b6d8b41b6b7a2d30a17918c5e
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spelling	oai:doaj.org-article:ee722c3b6d8b41b6b7a2d30a17918c5e2021-11-12T17:19:51ZSerum Predose Metabolic Profiling for Prediction of Rosuvastatin Pharmacokinetic Parameters in Healthy Volunteers1663-981210.3389/fphar.2021.752960https://doaj.org/article/ee722c3b6d8b41b6b7a2d30a17918c5e2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.752960/fullhttps://doaj.org/toc/1663-9812Rosuvastatin is a well-known lipid-lowering agent generally used for hypercholesterolemia treatment and coronary artery disease prevention. There is a substantial inter-individual variability in the absorption of statins usually caused by genetic polymorphisms leading to a variation in the corresponding pharmacokinetic parameters, which may affect drug therapy safety and efficacy. Therefore, the investigation of metabolic markers associated with rosuvastatin inter-individual variability is exceedingly relevant for drug therapy optimization and minimizing side effects. This work describes the application of pharmacometabolomic strategies using liquid chromatography coupled to mass spectrometry to investigate endogenous plasma metabolites capable of predicting pharmacokinetic parameters in predose samples. First, a targeted method for the determination of plasma concentration levels of rosuvastatin was validated and applied to obtain the pharmacokinetic parameters from 40 enrolled individuals; then, predose samples were analyzed using a metabolomic approach to search for associations between endogenous metabolites and the corresponding pharmacokinetic parameters. Data processing using machine learning revealed some candidates including sterols and bile acids, carboxylated metabolites, and lipids, suggesting the approach herein described as promising for personalized drug therapy.Anne Michelli Reis SilveiraGustavo Henrique Bueno DuarteAnna Maria Alves de Piloto FernandesPedro Henrique Dias GarciaNelson Rogerio VieiraMarcia Aparecida AntonioPatricia de Oliveira CarvalhoFrontiers Media S.A.articlepersonalized medicinemetabolomicsrosuvastatinpredictionmachine learningpharmacometabolomicsTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	personalized medicine metabolomics rosuvastatin prediction machine learning pharmacometabolomics Therapeutics. Pharmacology RM1-950
spellingShingle	personalized medicine metabolomics rosuvastatin prediction machine learning pharmacometabolomics Therapeutics. Pharmacology RM1-950 Anne Michelli Reis Silveira Gustavo Henrique Bueno Duarte Anna Maria Alves de Piloto Fernandes Pedro Henrique Dias Garcia Nelson Rogerio Vieira Marcia Aparecida Antonio Patricia de Oliveira Carvalho Serum Predose Metabolic Profiling for Prediction of Rosuvastatin Pharmacokinetic Parameters in Healthy Volunteers
description	Rosuvastatin is a well-known lipid-lowering agent generally used for hypercholesterolemia treatment and coronary artery disease prevention. There is a substantial inter-individual variability in the absorption of statins usually caused by genetic polymorphisms leading to a variation in the corresponding pharmacokinetic parameters, which may affect drug therapy safety and efficacy. Therefore, the investigation of metabolic markers associated with rosuvastatin inter-individual variability is exceedingly relevant for drug therapy optimization and minimizing side effects. This work describes the application of pharmacometabolomic strategies using liquid chromatography coupled to mass spectrometry to investigate endogenous plasma metabolites capable of predicting pharmacokinetic parameters in predose samples. First, a targeted method for the determination of plasma concentration levels of rosuvastatin was validated and applied to obtain the pharmacokinetic parameters from 40 enrolled individuals; then, predose samples were analyzed using a metabolomic approach to search for associations between endogenous metabolites and the corresponding pharmacokinetic parameters. Data processing using machine learning revealed some candidates including sterols and bile acids, carboxylated metabolites, and lipids, suggesting the approach herein described as promising for personalized drug therapy.
format	article
author	Anne Michelli Reis Silveira Gustavo Henrique Bueno Duarte Anna Maria Alves de Piloto Fernandes Pedro Henrique Dias Garcia Nelson Rogerio Vieira Marcia Aparecida Antonio Patricia de Oliveira Carvalho
author_facet	Anne Michelli Reis Silveira Gustavo Henrique Bueno Duarte Anna Maria Alves de Piloto Fernandes Pedro Henrique Dias Garcia Nelson Rogerio Vieira Marcia Aparecida Antonio Patricia de Oliveira Carvalho
author_sort	Anne Michelli Reis Silveira
title	Serum Predose Metabolic Profiling for Prediction of Rosuvastatin Pharmacokinetic Parameters in Healthy Volunteers
title_short	Serum Predose Metabolic Profiling for Prediction of Rosuvastatin Pharmacokinetic Parameters in Healthy Volunteers
title_full	Serum Predose Metabolic Profiling for Prediction of Rosuvastatin Pharmacokinetic Parameters in Healthy Volunteers
title_fullStr	Serum Predose Metabolic Profiling for Prediction of Rosuvastatin Pharmacokinetic Parameters in Healthy Volunteers
title_full_unstemmed	Serum Predose Metabolic Profiling for Prediction of Rosuvastatin Pharmacokinetic Parameters in Healthy Volunteers
title_sort	serum predose metabolic profiling for prediction of rosuvastatin pharmacokinetic parameters in healthy volunteers
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/ee722c3b6d8b41b6b7a2d30a17918c5e
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Serum Predose Metabolic Profiling for Prediction of Rosuvastatin Pharmacokinetic Parameters in Healthy Volunteers

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