Gemfibrozil pharmacokinetics

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. 

Preliminaiy evidence suggests that rifampicin can reduce the plasma levels of the active metabolite of clofibrate, but rifampicin apparently has no effect on gemfibrozil pharmacokinetics. 

Niemi M, Backman JT, Neuvonen M, Neuvonen PJ. Effects of gemfibrozil, itraconazole, and their combination on the pharmacokinetics and pharmacodynamics of repaglinide potentially hazardous interaction between gemfibrozil and repaglinide. Diabetologia 2003 46(3) 347-51. 

Niemi M, Neuvonen PJ, Kivisto KT. Effect of gemfibrozil on the pharmacokinetics and pharmacodynamics of glimepiride. Clin Pharmacol Ther 2001 70(5) 439-45. 

In contrast, although in vitro studies have not shown any evidence of pharmacokinetic interactions between cerivastatin and gemfibrozil (77), there was myalgia and a marked increase in creatine kinase in a 74-year-old woman with normal renal function who took gemfibrozil 1200 mg/day 3 weeks after she started to take cerivastatin 0.3 mg/day (78). 

Pharmacokinetics Both drugs are completely absorbed after an oral dose. Clofibrate is deesterified to the active clofibric acid, which binds to albumin and distributes widely in body tissues. Likewise, gemfibrozil distributes extensively, bound to albumin. Both drugs undergo extensive biotransformation and are excreted in the urine as their glucuronide conjugates. 

For instance/ the interaction between cerivastatin and gemfibrozil/ which has resulted in cases of severe rhabdomyolysiS/ is likely due to the inhibition of cerivastatin metabolism by gemfibrozil (i.e./ pharmacokinetic interaction)/ in addition to the propensity of both drugs to cause skeletal muscle toxicity (i.e./ pharmacodynamic interaction) (13-15). 

Mathew, P., Cuddy, T. and Tracewell, W.G. (2004) An open-label study on the pharmacokinetics (PK) of pitavastatin (NK-104) when administered concomitantly with fenofibrate or gemfibrozil in healthy volunteers (abstract PI-115). Clinical Pharmacology and Therapeutics, 75, 33. 

Vittal, S., Shitut, N.R., Kumar, T.R. et al. (2006) Simultaneous quantitation of rosuvastatin and gemfibrozil in human plasma by high-performance liquid chromatography and its application to a pharmacokinetic study. Biomed Chrom, 20 (11), 1252-1259. 

Sallustio, B.C. Foster, D.J.R. Reactivity of gemfibrozil l-O- -acyl glucuronide. Pharmacokinetics of covalently bound gemfibrozil-protein adducts in rats. Drug Metab.Dispos., 1995, 23, 892-899... 

TABLE 5.7 Effect of gemfibrozil and itraconazole on the pharmacokinetics of two insulin secretogogues."... 

Niemi M, Backman JT, Juntti-Patinen L, Neuvonen M, Neuvonen PJ. Coadministration of gemfibrozil and itraconazole has only a minor effect on the pharmacokinetics of the CYP2C9 and CYP3A4 substrate nateglinide. Br J Clin Pharmacol 2005 60 208 117. 

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