ROLE OF P GLYCOPROTEIN IN CATIONIC RENAL TUBULAR SECRETION

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Both cationic and p-glycoprotein mediated pathways are important mechanisms of tubular secretion within the kidney. These pathways are suseptible to competition by compounds that share common secretory pathways of renal clearance. Patients receiving a concomitant drugs that undergo extensive tubular secretion may be at risk for renal drug interactions which may result in drug toxicity. The contribution of p-glycoprotein transport in the renal clearance of the commonly used cations famotidine and cimetidine will be determined using itraconazole, a potent invitro p-glycoprotein inhibitor. If inhibition of p-glycoprotein results in a significant reduction in famotidine or cimetidine renal clearance the saturability of the cationic pathway could be explored in the presence of p-glycoprotein inhibition. If successful, this would allow the use of this agent as a probe of cationic and p-glycoprotein function.