Format

Send to

Choose Destination
Cancer Chemother Pharmacol. 2011 Mar;67(3):695-703. doi: 10.1007/s00280-010-1367-0. Epub 2010 May 29.

Marginal increase of sunitinib exposure by grapefruit juice.

Author information

1
Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands. p.h.van_erp@lumc.nl

Abstract

PURPOSE:

The drug label of sunitinib includes a warning for concomitant use of grapefruit juice (GJ) but clinical evidence for this drug interaction is lacking. The aim of this study is to determine the effect of GJ, a potent intestinal cytochrome P450 (CYP) 3A4 inhibitor, on steady-state sunitinib pharmacokinetics (PK).

METHODS:

Sunitinib PK was evaluated in eight cancer patients receiving sunitinib monotherapy in a "4 weeks on-2 weeks off" dose regimen. Serial blood samples for PK analysis of sunitinib were collected on two separate days. On both PK days, patients received a single oral dose of 7.5-mg midazolam as a phenotypic probe for assessment of intestinal CYP3A4 activity. The first PK day was at steady-state sunitinib PK (between days 14-20), the second PK day was on day 28. On days 25, 26 and 27, 200-mL GJ was consumed 3 times a day. The effect of GJ on sunitinib exposure was assessed by comparing sunitinib PK with and without GJ.

RESULTS:

Concomitant use of GJ and sunitinib resulted in an 11% increase of the relative bioavailability of sunitinib (P < 0.05). The effect of GJ on CYP3A4 activity was confirmed by an increase of ~50% of mean midazolam exposure (AUC(0-24 h)) from 122.1 to 182.0 ng h/mL (P = 0.034).

CONCLUSION:

GJ consumption results in a marginal increase in sunitinib exposure which is not considered clinically relevant. There is no clinical evidence underscoring the warning in the sunitinib drug label regarding concomitant use of GJ.

PMID:
20512335
PMCID:
PMC3043256
DOI:
10.1007/s00280-010-1367-0
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Springer Icon for PubMed Central
Loading ...
Support Center