Modulation of erlotinib pharmacokinetics in mice by a novel cytochrome P450 3A4 inhibitor, BAS 100.
Administration of BAS 100, a novel mechanism-based CYP3A4 inhibitor isolated from grapefruit juice, resulted in a 2.1-fold increase in erlotinib exposure following oral administration to wild-type and humanized CYP3A4 transgenic mice. This study illustrates the potential of BAS 100 to increase the low and variable oral bioavailability of erlotinib in cancer patients.
Smith
N F
NF
Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Baker
S D
SD
Gonzalez
F J
FJ
Harris
J W
JW
Figg
W D
WD
Sparreboom
A
A
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001628:Beverages; D001682:Biological Availability; D032083:Citrus paradisi; D065692:Cytochrome P-450 CYP3A Inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D000069347:Erlotinib Hydrochloride; D004952:Esters / Q000494:pharmacology*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011799:Quinazolines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011897:Random Allocation; D013141:Spiro Compounds / Q000494:pharmacology*
D000970:Antineoplastic Agents; C529377:BAS 100; D065692:Cytochrome P-450 CYP3A Inhibitors; D004791:Enzyme Inhibitors; D004952:Esters; C487471:OSI-420; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D013141:Spiro Compounds; D000069347:Erlotinib Hydrochloride