Stable isotope-labelled intravenous microdose for absolute bioavailability and effect of grapefruit juice on ibrutinib in healthy adults.

ABSTRACT:

Aims

Ibrutinib, an inhibitor of Bruton's tyrosine kinase, is used in the treatment of mantle cell lymphoma or chronic lymphocytic leukaemia. Ibrutinib undergoes extensive rapid oxidative metabolism mediated by cytochrome P450 3A both at the level of first pass and clearance, which might result in low oral bioavailability. The present study was designed to investigate the absolute bioavailability (F) of ibrutinib in the fasting and fed state and assess the effect of grapefruit juice (GFJ) on the systemic exposure of ibrutinib in order to determine the fraction escaping the gut (Fg ) and the fraction escaping hepatic extraction (Fh ) in the fed state.

Methods

All participants received treatment A [560 mg oral ibrutinib, under fasting conditions], B (560 mg PO ibrutinib, fed, a

SUBMITTER: de Vries R 

PROVIDER: S-EPMC4833163 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature