Comparison of Population Pharmacokinetics Based on Steady-State Assumption Versus Electronically Monitored Adherence to Lopinavir, Atazanavir, Efavirenz, and Etravirine: A Retrospective Study.

Details

Serval ID
serval:BIB_9C5EDAE96F2A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Comparison of Population Pharmacokinetics Based on Steady-State Assumption Versus Electronically Monitored Adherence to Lopinavir, Atazanavir, Efavirenz, and Etravirine: A Retrospective Study.
Journal
Therapeutic drug monitoring
Author(s)
Fuchs A., Rotzinger A., Cavassini M., Bugnon O., Buclin T., Schneider M.P., Csajka C.
ISSN
1536-3694 (Electronic)
ISSN-L
0163-4356
Publication state
Published
Issued date
08/2016
Peer-reviewed
Oui
Volume
38
Number
4
Pages
506-515
Language
english
Notes
Publication types: Journal Article ; Observational Study
Publication Status: ppublish
Abstract
Population pharmacokinetic (PopPK) analyses often rely on steady state and full adherence to prescribed dosage regimen assumptions from data gathered during therapeutic drug monitoring (TDM). Nonadherence is common in chronic diseases such as HIV. This study evaluates the impact of adherence measurement by electronic monitoring on PopPK parameter estimation and individual concentration profile predictions, and also the influence of adherence issues on the clinical interpretation of a concentration measurement.
Published PopPK models for lopinavir, atazanavir, efavirenz, and etravirine were applied to estimate PK parameters and individual concentrations in 140 HIV patients taking part in a medication adherence program using 2 dosing data sets. The first set included the last dose reported by the patient with steady-state and full adherence assumptions; the second set used detailed electronic dosing history. PopPK parameter estimates and individual predictions were compared between the 2 dosing entries.
Clearance estimates and likewise predicted concentrations did not markedly differ between the 2 dosing histories. However, certain patterns of nonadherence such as sparse missed doses or consecutive missed doses lead to suboptimal drug exposure. The interpretation based on self-reported information would have concluded on a wrongly appropriate individual exposure.
PopPK analysis assuming steady state with full adherence produced similar results to those based on detailed electronic dosing history reconciled with patients' allegations. Self-reported last dose intake appeared reliable for concentration predictions and therapeutic drug monitoring interpretation for most patients followed at the medication adherence program. Yet, clinicians should be aware that concentration predictions based on self-reported last dose intake might be overestimated in case of undetected patterns of nonadherence, increasing the risk of forthcoming therapeutic failure.

Keywords
Atazanavir Sulfate/blood, Atazanavir Sulfate/pharmacokinetics, Atazanavir Sulfate/therapeutic use, Benzoxazines/blood, Benzoxazines/pharmacokinetics, Benzoxazines/therapeutic use, Drug Monitoring/methods, HIV Infections/drug therapy, HIV Protease Inhibitors/blood, HIV Protease Inhibitors/pharmacokinetics, Humans, Lopinavir/blood, Lopinavir/pharmacokinetics, Lopinavir/therapeutic use, Medication Adherence, Pyridazines/blood, Pyridazines/pharmacokinetics, Pyridazines/therapeutic use, Retrospective Studies, Reverse Transcriptase Inhibitors/blood, Reverse Transcriptase Inhibitors/pharmacokinetics, Reverse Transcriptase Inhibitors/therapeutic use
Pubmed
Web of science
Create date
10/03/2016 19:47
Last modification date
20/08/2019 16:03
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