Population Pharmacokinetic Modeling to Inform Sertraline Dosing Optimization in Patients with Depression.
Pharmacology
; 108(4): 409-415, 2023.
Article
em En
| MEDLINE
| ID: mdl-37257430
Sertraline is one of the most prescribed antidepressants, but its pharmacokinetic (PK) properties are still not completely characterized. Using nonlinear mixed-effects modeling, we examined factors influencing sertraline PK variability in outpatients with major depressive disorder. Blood samples from 53 male and female adults treated with sertraline orally were collected at a steady state. Various demographic and clinical covariates were tested by stepwise regression procedure. We found that sertraline clearance is significantly influenced by serum concentrations of its main metabolite N-desmethylsertraline, whereas clearance of N-desmethylsertraline is affected by both creatinine clearance and drug daily dose. These results were confirmed by the reduction of points dispersion in goodness-of-fit plots for their predicted versus measured concentrations and with bootstrapping analyses. This finding can serve to inform sertraline dosing optimization, especially when changes in kidney function occur in treated individuals, to prevent adverse drug reactions and maximize therapeutic benefits.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sertralina
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Transtorno Depressivo Maior
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article