Interaction between fibrates and statins--metabolic interactions with gemfibrozil.
An in vitro study was carried out in order to examine the metabolic basis of the interaction between fibrates and statins. Metabolic inhibition of statins was noted in the presence of gemfibrozil. However, increase in the unchanged form was fairly small for pitavastatin, compared with other statins. Several CYP enzymes were shown to be principally responsible for the metabolism of gemfibrozil in contrast to other fibrates. In the presence of gemfibrozil, a focal point was obtained in Dixon plots, demonstrating that there was inhibition of CYP2C8-, CYP2C9- and CYP3A4-mediated metabolism. We propose that the increase of plasma concentration caused by co-administration of gemfibrozil and statins is at least partially due to CYP-mediated inhibition.
Fujino
Hideki
H
Tokyo New Drug Research Laboratories I, Kowa Company Ltd., Higashimurayama, Tokyo, Japan. h-fujino@kowa.co.jp
Yamada
Iwao
I
Shimada
Shimada
S
Hirano
Masaru
M
Tsunenari
Yoshihiko
Y
Kojima
Junji
J
D000069059:Atorvastatin; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015248:Gemfibrozil / Q000378:metabolism* / Q000494:pharmacology; D006538:Heptanoic Acids / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism*; D011725:Pyridines / Q000378:metabolism; D011758:Pyrroles / Q000378:metabolism; D011804:Quinolines / Q000378:metabolism
D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011725:Pyridines; D011758:Pyrroles; D011804:Quinolines; D003577:Cytochrome P-450 Enzyme System; D000069059:Atorvastatin; C086276:cerivastatin; C108475:pitavastatin; D015248:Gemfibrozil