What should patients do if they miss a dose of medication? A theoretical approach.
Levothyroxine
Medication adherence
Missed doses
Stochastics
Journal
Journal of pharmacokinetics and pharmacodynamics
ISSN: 1573-8744
Titre abrégé: J Pharmacokinet Pharmacodyn
Pays: United States
ID NLM: 101096520
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
received:
08
02
2021
accepted:
17
08
2021
pubmed:
11
9
2021
medline:
17
3
2022
entrez:
10
9
2021
Statut:
ppublish
Résumé
Medication adherence is a major problem for patients with chronic diseases that require long term pharmacotherapy. Many unanswered questions surround adherence, including how adherence rates translate into treatment efficacy and how missed doses of medication should be handled. To address these questions, we formulate and analyze a mathematical model of the drug concentration in a patient with imperfect adherence. We find exact formulas for drug concentration statistics, including the mean, the coefficient of variation, and the deviation from perfect adherence. We determine how adherence rates translate into drug concentrations, and how this depends on the drug half-life, the dosing interval, and how missed doses are handled. While clinical recommendations require extensive validation and should depend on drug and patient specifics, as a general principle our theory suggests that nonadherence is best mitigated by taking double doses following missed doses if the drug has a long half-life. This conclusion contradicts some existing recommendations that cite long drug half-lives as the reason to avoid a double dose after a missed dose. Furthermore, we show that a patient who takes double doses after missed doses can have at most only slightly more drug in their body than a perfectly adherent patient if the drug half-life is long. We also investigate other ways of handling missed doses, including taking an extra fractional dose following a missed dose. We discuss our results in the context of hypothyroid patients taking levothyroxine.
Identifiants
pubmed: 34506001
doi: 10.1007/s10928-021-09777-6
pii: 10.1007/s10928-021-09777-6
doi:
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
873-892Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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