A pharmacokinetics‐based approach to the monitoring of patient adherence to atorvastatin therapy

Abstract The inadequate adherence of patients whose hyperlipidemia is treated with atorvastatin (ATR) to medical instructions presents a serious health risk. Our aim was to develop a flexible approach based on therapeutic drug monitoring (TDM), nonparametric population pharmacokinetic modeling, and...

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Autores principales:	Gellért Balázs Karvaly, István Karádi, István Vincze, Michael N. Neely, Eszter Trojnár, Zoltán Prohászka, Éva Imreh, Barna Vásárhelyi, András Zsáry
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	adherence atorvastatin metabolism nonparametric pharmacokinetic model pharmacokinetics therapeutic drug monitoring Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/e3277a6d16c34a73b9a26ecfca0b40fd
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spelling	oai:doaj.org-article:e3277a6d16c34a73b9a26ecfca0b40fd2021-11-16T13:45:55ZA pharmacokinetics‐based approach to the monitoring of patient adherence to atorvastatin therapy2052-170710.1002/prp2.856https://doaj.org/article/e3277a6d16c34a73b9a26ecfca0b40fd2021-10-01T00:00:00Zhttps://doi.org/10.1002/prp2.856https://doaj.org/toc/2052-1707Abstract The inadequate adherence of patients whose hyperlipidemia is treated with atorvastatin (ATR) to medical instructions presents a serious health risk. Our aim was to develop a flexible approach based on therapeutic drug monitoring (TDM), nonparametric population pharmacokinetic modeling, and Monte Carlo simulation to differentiate adherent patients from partially and nonadherent individuals in a nonrandomized, unicentric, observational study. Sixty‐five subjects were enrolled. Nonparametric, mixed‐effect population pharmacokinetic models of the sums of atorvastatin and atorvastatin lactone concentrations (ATR+ATRL) and of the concentrations of the acid and lactone forms of ATR and its 2‐ and 4‐hydroxylated pharmacologically active metabolites (ATR+MET) were elaborated by including the TDM results obtained in 128 samples collected from thirty‐nine subjects. Monte Carlo simulation was performed based on the elaborated models to establish the probabilities of attaining a specific ATR+ATRL or ATR+MET concentration in the range of 0.002–10 nmol (mg dose)−1 L−1 at 1–24 h postdose by adherent, partially adherent, and nonadherent patients. The results of the simulations were processed to allow the estimation of the adherence of further 26 subjects who were phlebotomized at sampling times of 2–20 h postdose by calculating the probabilities of attaining the ATR+ATRL and ATR+MET concentrations measured in these subjects in adherent, partially adherent, and nonadherent individuals. The best predictive values of the estimates of adherence could be obtained with sampling at early sampling times. 61.54% and 38.46% of subjects in the adherence testing set were estimated to be fully and partially adherent, respectively, while in all cases the probability of nonadherence was extremely low. The evaluation of patient adherence to ATR therapy based on pharmacokinetic modeling and Monte Carlo simulation has important advantages over the collection of trough samples and the use of therapeutic ranges.Gellért Balázs KarvalyIstván KarádiIstván VinczeMichael N. NeelyEszter TrojnárZoltán ProhászkaÉva ImrehBarna VásárhelyiAndrás ZsáryWileyarticleadherenceatorvastatinmetabolismnonparametric pharmacokinetic modelpharmacokineticstherapeutic drug monitoringTherapeutics. PharmacologyRM1-950ENPharmacology Research & Perspectives, Vol 9, Iss 5, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	adherence atorvastatin metabolism nonparametric pharmacokinetic model pharmacokinetics therapeutic drug monitoring Therapeutics. Pharmacology RM1-950
spellingShingle	adherence atorvastatin metabolism nonparametric pharmacokinetic model pharmacokinetics therapeutic drug monitoring Therapeutics. Pharmacology RM1-950 Gellért Balázs Karvaly István Karádi István Vincze Michael N. Neely Eszter Trojnár Zoltán Prohászka Éva Imreh Barna Vásárhelyi András Zsáry A pharmacokinetics‐based approach to the monitoring of patient adherence to atorvastatin therapy
description	Abstract The inadequate adherence of patients whose hyperlipidemia is treated with atorvastatin (ATR) to medical instructions presents a serious health risk. Our aim was to develop a flexible approach based on therapeutic drug monitoring (TDM), nonparametric population pharmacokinetic modeling, and Monte Carlo simulation to differentiate adherent patients from partially and nonadherent individuals in a nonrandomized, unicentric, observational study. Sixty‐five subjects were enrolled. Nonparametric, mixed‐effect population pharmacokinetic models of the sums of atorvastatin and atorvastatin lactone concentrations (ATR+ATRL) and of the concentrations of the acid and lactone forms of ATR and its 2‐ and 4‐hydroxylated pharmacologically active metabolites (ATR+MET) were elaborated by including the TDM results obtained in 128 samples collected from thirty‐nine subjects. Monte Carlo simulation was performed based on the elaborated models to establish the probabilities of attaining a specific ATR+ATRL or ATR+MET concentration in the range of 0.002–10 nmol (mg dose)−1 L−1 at 1–24 h postdose by adherent, partially adherent, and nonadherent patients. The results of the simulations were processed to allow the estimation of the adherence of further 26 subjects who were phlebotomized at sampling times of 2–20 h postdose by calculating the probabilities of attaining the ATR+ATRL and ATR+MET concentrations measured in these subjects in adherent, partially adherent, and nonadherent individuals. The best predictive values of the estimates of adherence could be obtained with sampling at early sampling times. 61.54% and 38.46% of subjects in the adherence testing set were estimated to be fully and partially adherent, respectively, while in all cases the probability of nonadherence was extremely low. The evaluation of patient adherence to ATR therapy based on pharmacokinetic modeling and Monte Carlo simulation has important advantages over the collection of trough samples and the use of therapeutic ranges.
format	article
author	Gellért Balázs Karvaly István Karádi István Vincze Michael N. Neely Eszter Trojnár Zoltán Prohászka Éva Imreh Barna Vásárhelyi András Zsáry
author_facet	Gellért Balázs Karvaly István Karádi István Vincze Michael N. Neely Eszter Trojnár Zoltán Prohászka Éva Imreh Barna Vásárhelyi András Zsáry
author_sort	Gellért Balázs Karvaly
title	A pharmacokinetics‐based approach to the monitoring of patient adherence to atorvastatin therapy
title_short	A pharmacokinetics‐based approach to the monitoring of patient adherence to atorvastatin therapy
title_full	A pharmacokinetics‐based approach to the monitoring of patient adherence to atorvastatin therapy
title_fullStr	A pharmacokinetics‐based approach to the monitoring of patient adherence to atorvastatin therapy
title_full_unstemmed	A pharmacokinetics‐based approach to the monitoring of patient adherence to atorvastatin therapy
title_sort	pharmacokinetics‐based approach to the monitoring of patient adherence to atorvastatin therapy
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/e3277a6d16c34a73b9a26ecfca0b40fd
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A pharmacokinetics‐based approach to the monitoring of patient adherence to atorvastatin therapy

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