TY - JOUR
T1 - Pharmacokinetics and pharmacodynamics of nilotinib in gastrointestinal stromal tumors
AU - Trent, Jonathan
AU - Molimard, Mathieu
N1 - Funding Information:
Publication of this article was supported by Novartis Pharmaceuticals Corporation .
Funding Information:
This work was supported by The GIST Cancer Research Fund (JCT). Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals. The authors thank Angelo Russo, PhD, for his medical editorial assistance with the manuscript.
PY - 2011/4
Y1 - 2011/4
N2 - Nilotinib is a second-generation, oral tyrosine kinase inhibitor that provides specific inhibition of KIT, platelet-derived growth factor receptors (PDGFRs) alpha and beta, as well as breakpoint cluster region Abelson. Studies in healthy volunteers and patients with chronic myelogenous leukemia or gastrointestinal stromal tumors (GIST) have shown that the pharmacokinetics (PK) of nilotinib are similar to those of imatinib and well suited to twice-daily administration of a 400-mg dose. These studies show that the maximum plasma concentration of nilotinib is reached 3 to 4 hours after oral administration, with an elimination half-life of 17 hours through metabolism via oxidation and hydroxylation. Bioavailability of nilotinib is increased if administered with a high-fat meal or with cytochrome P450 3A4 inhibitors, but consumption of high-fat meals to allow lower doses of nilotinib is not recommended. Proton pump inhibitors have not been shown to have a clinically significant impact on nilotinib PK. Several studies have demonstrated preliminary evidence that nilotinib provides clinical benefit and can be safely administered to imatinib-resistant GIST patients.
AB - Nilotinib is a second-generation, oral tyrosine kinase inhibitor that provides specific inhibition of KIT, platelet-derived growth factor receptors (PDGFRs) alpha and beta, as well as breakpoint cluster region Abelson. Studies in healthy volunteers and patients with chronic myelogenous leukemia or gastrointestinal stromal tumors (GIST) have shown that the pharmacokinetics (PK) of nilotinib are similar to those of imatinib and well suited to twice-daily administration of a 400-mg dose. These studies show that the maximum plasma concentration of nilotinib is reached 3 to 4 hours after oral administration, with an elimination half-life of 17 hours through metabolism via oxidation and hydroxylation. Bioavailability of nilotinib is increased if administered with a high-fat meal or with cytochrome P450 3A4 inhibitors, but consumption of high-fat meals to allow lower doses of nilotinib is not recommended. Proton pump inhibitors have not been shown to have a clinically significant impact on nilotinib PK. Several studies have demonstrated preliminary evidence that nilotinib provides clinical benefit and can be safely administered to imatinib-resistant GIST patients.
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U2 - 10.1053/j.seminoncol.2011.01.014
DO - 10.1053/j.seminoncol.2011.01.014
M3 - Article
C2 - 21419933
AN - SCOPUS:79952770929
VL - 38
SP - S28-S33
JO - Seminars in Oncology
JF - Seminars in Oncology
SN - 0093-7754
IS - 1 SUPPL.
ER -