Effect of grapefruit juice on the pharmacokinetics of nilotinib in healthy participants.
J Clin Pharmacol
; 50(2): 188-94, 2010 Feb.
Article
en En
| MEDLINE
| ID: mdl-19948946
ABSTRACT
Nilotinib (Tasigna; Novartis Pharmaceuticals) is a second-generation BCR-ABL tyrosine kinase inhibitor newly approved for the treatment of imatinib-resistant or imatinib-intolerant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia in chronic phase or accelerated phase. This study evaluated the effect of grapefruit juice on the pharmacokinetics of nilotinib in 21 healthy male participants. All participants underwent 2 study periods during which they received a single oral dose of 400 mg nilotinib with 240 mL double-strength grapefruit juice or 240 mL water in a crossover fashion. Serial blood samples were collected for the determination of serum nilotinib concentrations by a validated liquid chromatography/tandem mass spectrometry assay. Concurrent intake of grapefruit juice increased the nilotinib peak concentration (C(max)) by 60% and the area under the serum concentration-time curve (AUC(0-infinity)) by 29% but did not affect the time to reach C(max) or the elimination half-life of nilotinib. The most common adverse events were headache and vomiting, which were mild or moderate in severity, and their frequency appeared to be similar between 2 treatments. Based on the currently available information about nilotinib and the observed extent of increase in nilotinib exposure, concurrent administration of nilotinib with grapefruit juice is not recommended.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Pirimidinas
/
Interacciones Alimento-Droga
/
Citrus paradisi
Tipo de estudio:
Clinical_trials
Límite:
Adolescent
/
Adult
/
Aged
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
J Clin Pharmacol
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos