EFFECTS OF DIETARY SALT INTAKE ON INTESTINAL CYP3A4 &P GLYCOPROTEIN

$206M01FY2000RRNIH

University Of Michigan At Ann Arbor, Ann Arbor MI

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Abstract

We have shown that the intestinal expression of P-glycoprotein and CYP3A4 and the liver expression of CYP3A4 are able to explain up to 75% of the oral kinetics of some drugs. It was recently reported that low dietary salt intake increased to oral absorption of quinidine, a routinely used antiarrhythmic. Since quinidine is a substrate for both P-glycoprotein and CYP3A4, we hypothesize that the effect of salt is due to changes in the level of expression of P-glycoprotein and/or CYP3A4. This study will directly test this hypothesis by measuring quinidine pharmacokinetics and P-glycoprotein and CYP3A4 levels in subjects placed on low and high salt diets.

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