Virtual twins for model-informed precision dosing of clozapine in patients with treatment-resistant schizophrenia.
CPT Pharmacometrics Syst Pharmacol
; 13(3): 424-436, 2024 03.
Article
em En
| MEDLINE
| ID: mdl-38243630
ABSTRACT
Model-informed precision dosing using virtual twins (MIPD-VTs) is an emerging strategy to predict target drug concentrations in clinical practice. Using a high virtualization MIPD-VT approach (Simcyp version 21), we predicted the steady-state clozapine concentration and clozapine dosage range to achieve a target concentration of 350 to 600 ng/mL in hospitalized patients with treatment-resistant schizophrenia (N = 11). We confirmed that high virtualization MIPD-VT can reasonably predict clozapine concentrations in individual patients with a coefficient of determination (R2 ) ranging between 0.29 and 0.60. Importantly, our approach predicted the final dosage range to achieve the desired target clozapine concentrations in 73% of patients. In two thirds of patients treated with fluvoxamine augmentation, steady-state clozapine concentrations were overpredicted two to four-fold. This work supports the application of a high virtualization MIPD-VT approach to inform the titration of clozapine doses in clinical practice. However, refinement is required to improve the prediction of pharmacokinetic drug-drug interactions, particularly with fluvoxamine augmentation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Esquizofrenia
/
Antipsicóticos
/
Clozapina
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
CPT Pharmacometrics Syst Pharmacol
Ano de publicação:
2024
Tipo de documento:
Article