Effect of CYP2D6 genotype on duloxetine serum concentration.
Basic Clin Pharmacol Toxicol
; 134(1): 186-192, 2024 Jan.
Article
en En
| MEDLINE
| ID: mdl-37864290
ABSTRACT
Duloxetine is metabolized by cytochrome P450 (CYP)1A2 and CYP2D6. The aim of this study was to investigate the effect of the CYP2D6 genotype on duloxetine serum concentration adjusting for age and sex. Patients were included retrospectively from a therapeutic drug monitoring service. Multiple linear regression analysis was used to investigate the effect of CYP2D6 genotype, age and sex on the duloxetine concentration-to-dose (C/D) ratio. In total, 269 patients were included and assigned to the following genotype-predicted phenotype subgroups CYP2D6 poor metabolizers (PMs, n = 23), intermediate metabolizers (IMs, n = 121), normal metabolizers (NMs, n = 120) and ultrarapid metabolizers (UMs, n = 5). Multiple linear regression analysis revealed a 95% higher duloxetine C/D ratio in PMs compared with NMs (p = 0.009). Patients ≥65 years had a 56% higher C/D ratio than younger patients (p = 0.01), while women had a 46% higher C/D ratio than men (p = 0.04). In conclusion, the CYP2D6 PM phenotype is associated with a twofold higher concentration at recommended dosing compared with the NM phenotype. CYP2D6 PM females above 65 years are at particular risk of high duloxetine levels as they may obtain a threefold higher C/D ratio compared with younger, male NMs.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Citocromo P-450 CYP2D6
Límite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Basic Clin Pharmacol Toxicol
Asunto de la revista:
FARMACOLOGIA
/
TOXICOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Noruega