Population pharmacokinetic analysis reveals no impact of aprepitant on the pharmacokinetics of ifosfamide, 2-dechloroifosfamide, and 3-dechloroifosfamide.
Eur J Pharm Sci
; 185: 106420, 2023 Jun 01.
Article
en En
| MEDLINE
| ID: mdl-36882147
ABSTRACT
PURPOSE:
Several case reports and retrospective series have clearly pointed to the role of aprepitant, an antiemetic drug, in the development of encephalopathy when used with ifosfamide. Described as an inhibitor of several CYP metabolic pathways, aprepitant is suspected of drug-drug-interaction on ifosfamide pharmacokinetics. The pharmacokinetics of ifosfamide and two of its metabolites (2-dechloroifosfamide and 3-dechloroifosfamide) was studied in patients with soft tissue sarcomas to evaluate the impact of aprepitant administration.METHODS:
A population pharmacokinetic approach was applied to analyze data obtained in 42 patients at cycle 1 (without aprepitant) and cycle 2 (with aprepitant for 34 of them).RESULTS:
A previously published pharmacokinetic model including a time-dependency process well fit the data. Aprepitant had no impact on ifosfamide or its two metabolite pharmacokinetic parameters.CONCLUSION:
This study suggests that aprepitant does not lead to a significant modification of ifosfamide metabolization, even though other metabolites such as 4 hydroxyifosfamide and chloroacetaldehyde were not monitored in this study.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Sarcoma
/
Antieméticos
Tipo de estudio:
Observational_studies
Límite:
Humans
Idioma:
En
Revista:
Eur J Pharm Sci
Asunto de la revista:
FARMACIA
/
FARMACOLOGIA
/
QUIMICA
Año:
2023
Tipo del documento:
Article
País de afiliación:
Francia