Procainamide pharmacokinetics in beagles: urinary pH dependency and comparison with n-acetylprocainamide.
Male and female beagles received intravenous (i.v.) bolus injections of procainamide (PA) to study its pharmacokinetic behavior and to determine the effect of urinary pH upon renal excretion. Urinary alkalinization caused an increase in plasma disappearance half-life (t1/2) and decreases in renal clearance (ClR) and total body clearance (ClB), while the apparent volume of distribution remained unchanged. Acid hydrolysis of the urine collected caused a 17% increase in the amount of PA measured. This hydrolyzable substance was found not to be the N-acetylated metabolite of PA. When i.v. N-acetylprocainamide (NAPA) was administered in crossover fashion to some of the above animals, it exhibited a longer t1/2 than PA. Mean ClR and mean ClB values were smaller with NAPA while both compounds showed similar dependence upon renal and non-renal clearance mechanisms.
Procainamide pharmacokinetics in beagles: urinary pH dependency and comparison with n-acetylprocainamide. Male and female beagles received intravenous (i.v.) bolus injections of procainamide (PA) to study its pharmacokinetic behavior and to determine the effect of urinary pH upon renal excretion. Urinary alkalinization caused an increase in plasma disappearance half-life (t1/2) and decreases in renal clearance (ClR) and total body clearance (ClB), while the apparent volume of distribution remained unchanged. Acid hydrolysis of the urine collected caused a 17% increase in the amount of PA measured. This hydrolyzable substance was found not to be the N-acetylated metabolite of PA. When i.v. N-acetylprocainamide (NAPA) was administered in crossover fashion to some of the above animals, it exhibited a longer t1/2 than PA. Mean ClR and mean ClB values were smaller with NAPA while both compounds showed similar dependence upon renal and non-renal clearance mechanisms.