Trimethoprim Inhibition of the Renal Clearance of Procainamide and N-Acetylprocainamide

Vlasses, Peter H.; Kosoglou, Teddy; Chase, Sandra L.; Greenspon, Arnold J.; Lottes, Sandra R.; Andress, Edie; Ferguson, Roger K.; Rocci, Mario L.

doi:10.1001/archinte.1989.00390060080016

Cited by 20 publications

(2 citation statements)

References 16 publications

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“…Trimethoprim is another basic drug that is renally secreted by organic cation transporters. 56 It is a 2,4diaminopyrimidine antibiotic and antiparasitic agent that is rapidly cleared by net tubular secretion. Concurrent administration with procainamide has been shown to lead to a marked elevation of the plasma concentrations of both drugs as well as N-acetylprocainamide.…”

Section: Drug Interactions With Organic Cation Transportersmentioning

confidence: 99%

“…Concurrent administration with procainamide has been shown to lead to a marked elevation of the plasma concentrations of both drugs as well as N-acetylprocainamide. 56 Other compounds, such as dipyridamole (a platelet inhibitor and vasodilator), have been shown to interact with the organic cation transport system in the kidney and reduce transcellular flux of other basic drugs. 57 Based on research with the H 2 -receptor antagonists, trimethoprim, and dipyridamole, it seems likely that many other cationic drugs can cause drug-drug interactions when coadministered.…”

Section: Drug Interactions With Organic Cation Transportersmentioning

confidence: 99%

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Renal Drug Transport and Drug-Drug Interactions

Ronaldson

Bendayan

2002

Journal of Pharmacy Practice

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The kidney plays a vital role in the elimination of xenobiotics including drugs, toxins, and endogenous metabolites. Renal drug elimination involves 3 major processes: glomerular filtration, tubular secretion, and tubular reabsorption. Although glomerular filtration is a simple unidirectional diffusion process, renal tubular secretion and/or reabsorption can involve saturable processes mediated by multiple highly specialized membrane transport systems. Current research has identified that these transport proteins play a significant role in the efficient removal and/or reabsorption of pharmacological agents. Since the majority of membrane transporters have broad substrate specificity, there is a significant risk for drug-drug interactions through competition for similar transport pathways. This article will focus on the cellular expression, localization, and transport properties of various renal drug transport systems (ie, organic anion, organic cation, nucleoside, and adenosine triphosphate [ATP]-dependent efflux transporters). Specific examples of drugs that are transported by each of these mechanisms will be provided. Clinically relevant drug-drug interactions involving renal drug transporters will be discussed to guide the clinician in understanding and preventing these interactions.

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Section: Drug Interactions With Organic Cation Transportersmentioning

confidence: 99%

Section: Drug Interactions With Organic Cation Transportersmentioning

confidence: 99%

Renal Drug Transport and Drug-Drug Interactions

Ronaldson

Bendayan

2002

Journal of Pharmacy Practice

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Effects of Ofloxacin on the Pharmacokinetics and Pharmacodynamics of Procainamide

Martin

Shen

Griener

et al. 1996

The Journal of Clinical Pharma

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Procainamide is a class I antiarrhythmic agent that undergoes active tubular secretion through the organic cation transport system, with approximately 50% of a dose excreted in the urine as unchanged drug. The remainder is metabolized to an active metabolite, n-acetyl procainamide (NAPA). Ofloxacin is a fluoroquinolone antibiotic that is excreted in the urine as unchanged drug via active tubular secretion and glomerular filtration. To test the hypothesis that ofloxacin may interfere with the renal elimination of procainamide, 9 healthy volunteers were randomly assigned to receive 1 g of oral procainamide as a single dose with or without pretreatment with 400 mg of ofloxacin twice a day for 5 doses. Blood and urine samples were obtained and pharmacokinetic parameters for procainamide were determined for each treatment period. Standard 12-lead and signal-averaged electrocardiographic recordings were used for pharmacodynamic analysis. The mean area under the concentration-time curve (AUC) and peak plasma concentration (Cmax; mug/mL) for procainamide increased by 27% and 21%, respectively, and the plasma clearance for procainamide decreased by an average of 22% with coadministration of ofloxacin. Ofloxacin did not significantly influence the pharmacokinetics of NAPA, nor were pharmacodynamics of procainamide significantly affected by coadministration of ofloxacin. These results suggest that procainamide concentrations should be monitored closely when coadministered with ofloxacin.

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Drug Interactions Involving Renal Excretory Mechanisms

Somogyi¹

1996

Mechanisms of Drug Interactions

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Trimethoprim Inhibition of the Renal Clearance of Procainamide and N-Acetylprocainamide

Cited by 20 publications

References 16 publications

Renal Drug Transport and Drug-Drug Interactions

Renal Drug Transport and Drug-Drug Interactions

Effects of Ofloxacin on the Pharmacokinetics and Pharmacodynamics of Procainamide

Drug Interactions Involving Renal Excretory Mechanisms

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