Cimetidine inhibits renal procainamide clearance

Area of Science:

• Pharmacology and Nephrology
• Drug Interactions and Renal Excretion

Background:

• Procainamide and cimetidine are primarily eliminated by renal excretion.
• Both drugs utilize active transport mechanisms in the proximal tubule for secretion.
• Pre-clinical studies indicate mutual inhibition of secretion between procainamide and cimetidine.

Purpose of the Study:

• To investigate the in-vivo effect of cimetidine on the renal clearance and pharmacokinetic parameters of procainamide in humans.
• To determine if cimetidine inhibits the active renal secretion of procainamide.

Main Methods:

• Human study assessing the impact of cimetidine administration on oral procainamide pharmacokinetics.
• Measurement of renal clearance, systemic clearance, bioavailability, elimination rate constant, and elimination half-life of procainamide.
• Analysis of the ratio of systemic clearance to bioavailability.

Main Results:

• Cimetidine significantly reduced the renal clearance of oral procainamide by 36%.
• Associated changes included an 18% decrease in the elimination rate constant and a 24% prolongation of elimination half-life.
• A 28% decrease was observed in the ratio of systemic clearance of procainamide to its bioavailability.

Conclusions:

• Cimetidine inhibits the active renal secretion of procainamide in humans.
• This inhibition leads to decreased systemic clearance and prolonged plasma half-life of procainamide.
• Highlights a clinically relevant drug interaction affecting renal drug elimination.