Ezetimibe pharmacokinetics

Kosoglou T, Statkevich P, Fruchart JC, Pember LJ, Reyderman L, Cutler DL, Guillaume M, Maxwell SE, Veltri EP. Pharmacodynamic and pharmacokinetic interaction between fenofibrate and ezetimibe. Curr Med Res Opin 2004 20(8) 1197-207. 

Ezzet F, Krishna G, Wexler DB, Statkevich P, Kosoglou T, Batra VK (2001) A population pharmacokinetic model that describes multiple peaks due to enterohepatic recirculation of ezetimibe. Clin Ther 23 871—885. 

The first liquid chromatography method introduced to determine ezetimibe and its metabolites was developed by Ezzet et al. [58], and the method was used to model the pharmacokinetics of ezetimibe in humans. The liquid chromatography-mass spectrometry (LC-MS) method was used to determine imchanged ezetimibe and total ezetimibe (imchanged ezetimibe together with ezetimibe glucoronide) in human plasma samples. 

Kosoglou T, Statkevich P, Johnson-Levonas AO, et al. Ezetimibe a review of its metabolism, pharmacokinetics, and drug interactions. Clin Pharmacokinet 2005 44 467-494. 

In a two-way, crossover study, 12 healthy subjects were given ezetimibe 10 mg or placebo daily for 11 days, with a single 25-mg dose of warfarin on day 7. The pharmacokinetics and pharmacodynamics (prothrombin time) of warfarin were not significantly altered by ezetimibe. In addition, the pharmacokinetics of ezetimibe were similar to those previously seen with the drug alone. However, the manufacturers of ezetimibe state that raised INRs have been seen in patients taking warfarin after they were also given ezetimibe. They therefore advise that the INR should be monitored if ezetimibe is given with any coumarin or fluindione, (this is probably a prudent precaution for any indanedione). 

In a study in 12 healthy subjects ezetimibe 10 mg daily for 7 days did not alter the pharmacokinetics of a single SOO-microgram dose of digoxin. In addition, ezetimibe did not alter the ECG effects of digoxin. ... 

No significant pharmacokinetic interaction appears to occur between ezetimibe and an ethinylestradiol/noigestrel-containing oral contraceptive. 

SimardC, TurgeonJ. The pharmacokinetics of ezetimibe. Can J Clin Pharmacol (2003) 10 (SupplA), 13A-20A. 

Ezetimibe does not alter fenoflbrate or gemfibrozil pharmacokinetics. Fenollbrate and gemfibrozil may modestly increase ezetimibe levels, although this is unlikely to be clinically relevant The manufacturers currently advise caution if ezetimibe is given with a flbrate, because of the theoretical increased risk of gallstone formation. 

Ezetimibe does not appear to have adverse pharmacokinetic interactions with atorvastatin, fluvastatin, iovastatin, rosuvastatin or simvastatin. However, some evidence suggests that concurrent use may increase the risk of myopathy. 

In a randomised, erossover study 32 otherwise healthy subjects with hy-pereholesterolaemia were given either ezetimibe 10 mg daily, fluvastatin 20 mg daily or both drugs in combination for 14 days. The combination was well tolerated, no significant pharmacokinetic interaction occurred, and an enhanced lowering of LDL-cholesterol was noted, which was considered to be clinically favourable. However, a case report describes a 52-year-old man taking fluvastatin 80 mg daily who developed elevated creatinine kinase levels 8 weeks after ezetimibe 10 mg daily was added. 

In a randomised, crossover study 18 healthy suhjeets were given either ezetimibe 10 mg daily, lovastatin 20 mg daily or both drugs in combination for 7 days. The combination was well tolerated, and no significant pharmacokinetic interaction was noted. ... 

In a three-arm study, patients were given simvastatin 80 mg daily, simvastatin 80 mg daily with ezetimibe 10 mg daily, or simvastatin 40 mg daily with ezetimibe 10 mg daily. No difference in adverse events was noted between each of the 3 groups and there were no significant elevations in creatine kinase. No cases of myopathy or rhabdomyolysis occurred, and the combination was well-tolerated. In another study, ezetimibe 0.25 mg, 1 mg or 10 mg daily had no effect on the pharmacokinetics of simvastatin 10 mg daily, when both were given for 14 days. In addition, 10 and 20-mg doses of simvastatin were well-tolerated in combination with ezetimibe. ... 

Reyderman L, Kosc lou T, Cutler DL, Ivbxwell, StatkevichP. The effect of fluvastatin on the pharmacokinetics and pharmacodynamics of ezetimibe. Curr MedRes Opin (2005) 21, 1171-9. 

Oswald S, Nassif A, Modess C, Keiser M, Hanke U, Engel A, Lutjohaim D, Weitschies W, Siegmund W. Pharmacokinetic and pharmacodynamic interactions between the immunosuppressant sirolimus and the lipid-lowering drug ezetimibe in healthy volunteers. Clin Pharmacol Ther 2010 87(6) 663-7. 

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