In vitro blood distribution and plasma protein binding of the tyrosine kinase inhibitor imatinib and its active metabolite, CGP74588, in rat, mouse, dog, monkey, healthy humans and patients with acute lymphatic leukaemia.

ABSTRACT:

Aims

To determine blood binding parameters of imatinib and its metabolite CGP74588 in humans and non-human species.

Methods

The blood distribution and protein binding of imatinib and CGP74588 were determined in vitro using (14)C labelled compounds.

Results

The mean fraction of imatinib in plasma (f(p)) was 45% in dog, 50% in mouse, 65% in rat, 70% in healthy humans and up to 92% in acute lymphatic leukaemia (AML) patients. Similarly, f(p) for CGP74588 was low in dog and monkey (30%), higher in rat, mouse and humans (70%) and highest in some AML patients (90%). The unbound fraction of imatinib and CGP74588 in plasma was lower in rat, mouse, healthy humans and AML patients (2.3-6.5% at concentrations < or = 5000 ng ml(-1)) compared to monkey and dog (7.6-19%). Both comp

SUBMITTER: Kretz O 

PROVIDER: S-EPMC1884586 | biostudies-literature | 2004 Aug

REPOSITORIES: biostudies-literature