Mechanistic studies on metabolic interactions between gemfibrozil and statins.

@article{Prueksaritanont2002MechanisticSO,
  title={Mechanistic studies on metabolic interactions between gemfibrozil and statins.},
  author={Thomayant Prueksaritanont and Jamie J. Zhao and Bennett Ma and Brad Roadcap and Cuyue Tang and Yue Qiu and Lida Liu and Jiunn Huei Lin and Paul G. Pearson and Thomas A. Baillie},
  journal={The Journal of pharmacology and experimental therapeutics},
  year={2002},
  volume={301 3},
  pages={
          1042-51
        }
}
A series of studies were conducted to explore the mechanism of the pharmacokinetic interaction between simvastatin (SV) and gemfibrozil (GFZ) reported recently in human subjects. After administration of a single dose of SV (4 mg/kg p.o.) to dogs pretreated with GFZ (75 mg/kg p.o., twice daily for 5 days), there was an increase (approximately 4-fold) in systemic exposure to simvastatin hydroxy acid (SVA), but not to SV, similar to the observation in humans. GFZ pretreatment did not increase the… Expand
Interconversion Pharmacokinetics of Simvastatin and its Hydroxy Acid in Dogs: Effects of Gemfibrozil
TLDR
In dogs, the interconversion process favored the formation of SVA and was less efficient than the irreversible elimination processes of SV and SVA, and Gemfibrozil treatment did not affect Vss,real of either SV or SVA. Expand
Effects of fibrates on metabolism of statins in human hepatocytes.
TLDR
The results suggest that there is a potential difference between fibrates in their ability to affect the pharmacokinetics of statins, and among statins in their susceptibility to metabolic interactions with GFZ in humans. Expand
Effect of Gemfibrozil on the Metabolism of Pitavastatin - Determining the Best Animal Model for Human CYP And UGT Activities
TLDR
It is concluded that the plasma level of pitavastatin would not be increased by co-administration of gemfibrozil in humans, and the best animal models for human CYP-mediated hydroxylation and UGT-mediated lactonization of pitvastatin were rats and dogs, respectively. Expand
Effect of a Single Gemfibrozil Dose on the Pharmacokinetics of Rosuvastatin in Bile and Plasma in Healthy Volunteers
TLDR
The value of monitoring the plasma pharmacokinetics of the inhibitor, and not only the drug under investigation, to improve the mechanistic interpretation is demonstrated, suggesting that the total plasma concentration of gemfibrozil needs to be above 20 μM to affect the disposition of rosuvastatin. Expand
Repaglinide-gemfibrozil drug interaction: inhibition of repaglinide glucuronidation as a potential additional contributing mechanism.
TLDR
It is demonstrated that repaglinide can undergo direct glucuronidation, a pathway that can possibly contribute to the interaction with gemfibrozil, and inhibition of UGT enzymes, especially UGT1A1, by gemfirzil and its glucuronide is an additional mechanism to consider when rationalizing the interaction between repagliide and gemf fibroZil. Expand
Gemfibrozil and its glucuronide inhibit the hepatic uptake of pravastatin mediated by OATP1B1
TLDR
It is hypothesized that gemfibrozil and the main plasma metabolites, a glucuronide and a carboxylic acid metabolite, might inhibit the hepatic uptake of pravastatin and lead to the elevation of the plasma concentration of pavastatin by the concomitant use of gem-glu. Expand
Inhibition of human organic anion transporter 3 mediated pravastatin transport by gemfibrozil and the metabolites in humans
TLDR
The inhibition of hOAT3-mediated pravastatin transport by gemfibrozil and its metabolites would lead to a decrease in the renal clearance of pravastsatin in clinical settings. Expand
Gemfibrozil inhibits CYP2C8-mediated cerivastatin metabolism in human liver microsomes.
TLDR
The present in vitro findings suggest that inhibition of CYP2C8 activity by gemfibrozil at least partially explains the interaction between gemf fibroziles and cerivastatin. Expand
GEMFIBROZIL INHIBITS CYP 2 C 8-MEDIATED CERIVASTATIN METABOLISM IN HUMAN LIVER MICROSOMES
To explore the mechanism of the interaction between gemfibrozil and cerivastatin, the enzyme mapping of the oxidative metabolism of cerivastatin and the effect of gemfibrozil on cerivastatinExpand
Comparative Effects of Fibrates on Drug Metabolizing Enzymes in Human Hepatocytes
TLDR
The results suggest that fibrates may have potential to cause various pharmacokinetic drug interactions via their differential effects on enzyme induction and/or inhibition. Expand
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