, Repaglinide, pioglitazone, rosiglitazone, loperamide and montelukast. The concomitant use of these drugs with gemfibrozil significantly increased Ht their AUC of cerivastatin in particular on five, seven or eight times, repaglinide, three to four times pioglitazone, rosiglitazone, two to three times, twice, loperamide and montelukast four to five times.

Chern Bafetinib INNO-406 in individual F, Especially those with CYP2C8 genotype quickly to Ausma it the interaction can significantly even hours be higher than the average. The extent This interaction is mainly due to the importance of CYP2C8 substrates in drug disposition. The inhibition of OATP1B1 by gemfibrozil may contribute to increased Hte exposure when the drug is also a victim of a substrate of this transporter. Some of the CYP2C8 substrates are also substrates of CYP3A4.
The inhibition of these enzymes can cause a serious interaction, particularly if the drug has a narrow therapeutic index substrate. A combination of two inhibitors of CYP3A4 and CYP2C8, such as gemfibrozil and itraconazole, a high exposure to 18 times and 13 times loperamide repaglinide. Gemfibrozil is not known to inhibit CYP enzymes other than CYP2C8 humans in vivo. Thus, gemfibrozil as an in vivo tool to be used to study the r The CYP2C8 in drug metabolism potential substrates. The effect of gemfibrozil on CYP2C8 in humans is fast and very long. Even a small dose of gemfibrozil in 1 h in an irreversible inactivation of CYP2C8, which lasts for mechanismbased 2 3 days after administration of gemfibrozil.
CYP2C8 activity recovered t only by de novo synthesis of new enzymes, which in humans has a half-life of turnover of approximately 22 h in vivo. Trimethoprim in vitro, a selective inhibitor of CYP2C8. In humans, trimethoprim increased the mean AUC of repaglinide Ht by 61% and 41% of pioglitazone, gemfibrozil is significantly lower. A sensitive probe CYP1A2 tizanidine tizanidine drug was used clinically for about 20 years before our group has demonstrated the importance of CYP1A2 in its metabolism to the test. Fluvoxamine causes a potentially found Hrlichen interactions with tizanidine, recd hung AUC by 33-fold and resulting in greatly reduced the systolic and diastolic blood pressure and above the Owned sedation. Ciprofloxacin, even when given with tizanidine increased its AUC increased more than tenfold, causing severe hypotension.
Also, oral contraceptives containing ethinyl estradiol and gestodene markedly increased Hen plasma concentrations and effects of tizanidine. Subsequent studies have also found rofecoxib is a potent inhibitor of the metabolism, dependent Ngig CYP1A2 in vitro. Rofecoxib increased Hte AUC of tizanidine 13-fold, with significant hypotensive and sedative effects. In all these studies, Ver Changes in plasma concentrations of tizanidine over the plasma caffeine / paraxanthine-money ratio, tizanidine are more sensitive than the ratio Ratio of caffeine / paraxanthine as an indicator of CYP1A2 activity t. The effect of rifampicin on the AUC of tizanidine was small, the poor inducibility of CYP1A2, especially if Drogenabh the strong effect of rifampicin on the AUC of numerous CYP3A4 Ngigen compared. Effect of fruit juice on the pharmacokinetics Since the