Erlotinib treatment induces cytochrome P450 3A activity in non-small cell lung cancer patients.
Br J Clin Pharmacol
; 85(8): 1704-1709, 2019 08.
Article
em En
| MEDLINE
| ID: mdl-30945322
ABSTRACT
AIMS:
Erlotinib is a tyrosine kinase inhibitor used in the treatment of non-small cell lung cancer highly metabolized by the cytochrome P450 (CYP) 3A. Hence, CYP3A4 activity might be a useful predictor of erlotinib pharmacokinetics in personalized medicine. The effect of erlotinib on CYP3A activity was therefore studied in non-small cell lung cancer patients.METHODS:
The study included 32 patients scheduled for erlotinib monotherapy. CYP3A activity was assessed using quinine as a probe before and during erlotinib treatment. Plasma from blood samples drawn 16 hours post quinine administration were analysed using HPLC with fluorescence detection to determine the quinine/3-OH-quinine ratio.RESULTS:
Matched samples, available from 13 patients, showed an induction of CYP3A activity (P = 0.003, Wilcoxon's signed rank test) after 2 months of treatment. The quinine/3-OH-quinine ratio decreased from 20.2 (± 13.4) at baseline to 11.0 (± 4.34). Single-point samples, available from 19 patients, supported the decrease in ratio (P = 0.007, Mann-Whitney U-test). Generally, females had a higher CYP3A activity both at baseline and after two months of treatment. Statistical analysis by gender also showed significant increase in CYP3A activity (males, n = 10, P = 0.001, and females, n = 22, P = 0.001).CONCLUSIONS:
An induction of CYP3A activity was observed after 2 months of erlotinib treatment which was also seen when subdividing based on gender. It could be important to take this into consideration for patients co-administering other CYP3A-metabolizing drugs during erlotinib treatment and also makes it difficult to use baseline CYP3A activity to predict erlotinib pharmacokinetics.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Pulmonar de Células não Pequenas
/
Inibidores de Proteínas Quinases
/
Citocromo P-450 CYP3A
/
Cloridrato de Erlotinib
/
Neoplasias Pulmonares
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Br J Clin Pharmacol
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Suécia