Mechanism-based inhibition of cytochrome P450 involves the bioactivation of the drug to a reactive metabolite, which leads to cytochrome inhibition via various mechanisms. This is generally seen in the Phase I of drug metabolism. However, gemfibrozil (hypolipidemic drug) leads to mechanism-based inhibition after generating glucuronide conjugate (gemfibrozil acyl-β-glucuronide) in the Phase II m...

Background: Familial combined hyperlipidaemia (FCH), characterized by elevated very-low-density lipoprotein (VLDL) and/or low-density lipoprotein (LDL), is associated with an increased prevalence of premature cardiovascular disease. Therefore, lipid-lowering is frequently indicated. Methods; We evaluated in a parallel, double-blind randomized fashion the effect of gemfibrozil (1200 mg/day) ( n ...

We investigated the hypocholesterolemic effects of lovastatin alone and in combination with gemfibrozil on plasma lipids and lipoproteins in 12 adult patients with well-characterized heterozygous familial hypercholesterolemia. Plasma concentrations of low density lipoprotein (LDL) cholesterol decreased from 321 +/- 14 mg/dl on diet only to 207 +/- 8 mg/dl (-35.5%) on single-drug therapy with lo...

Protein Levels in Abdominally Obese Men With the Atherogenic Dyslipidemia of the Metabolic Syndrome To the Editor: Recent data from Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial (VA-HIT) have recently reported that pharmacological treatment with a fibrate (gemfibrozil) significantly reduced coronary heart disease (CHD) risk among men with a history of CHD who had low ...

BACKGROUND Postprandial lipemia is associated with endothelial dysfunction. Remnant-like particles (RLP) have been suggested to contribute to these adverse vascular effects. We investigated the effect of cerivastatin and gemfibrozil upon oral fat load induced changes in endothelial function and postprandial lipid profile in vivo. METHODS In a randomized cross-over trial, 15 healthy volunteers...

The effect of gemfibrozil on the fine structure of peroxisomes across the rat liver lobule was investigated by light and electron microscopy using the alkaline diaminobenzidine (DAB) medium for the visualization of catalase peroxidatic activity. The oral administration of gemfibrozil for 2 weeks induces a striking heterogeneity in the lobular distribution of peroxisomes. The size and shape of p...

The risk assessment of organic anion transporting polypeptide (OATP) 1B1-mediated drug-drug interactions (DDIs) is an indispensable part of drug development. We previously reported that in vitro inhibitory potencies of several inhibitors on OATP1B1 depend on the substrates when prototypical substrates, estradiol-17β-glucuronide (E₂G), estrone-3-sulfate, and sulfobromophthalein were used as test...