Reduced quinidine clearance in elderly persons

The influence of age on quinidine pharmacokinetics was assessed in 22 healthy male and female volunteers; 14 of the subjects were young (aged 23 to 34 years) and 8 elderly (aged 60 to 69 years). All subjects received 180 to 300 mg of quinidine base by constant rate intravenous infusion over 10 to 15 minutes. The concentration of total and unbound quinidine in multiple serum samples and in urine collected within 48 hours after the administration of quinidine qas determined with spectrophotofluorometric assay. Mean kinetic values for total quinidine in the young subjects were: elimination half-life (t 1/2 beta), 7.3 hours; total volume of distribution (Vd), 2.39 liters/kg; total clearance, 4.04 ml/min per kg; renal clearance 1.43 ml/min per kg; and percent unbound, 24.6 In the elderly subjects, the values for Vd (2.18 liters/kg) and percent unbound (28.2) did not differ significantly from these values in the young subjects. However, in the elderly subjects t 1/2 beta was significantly longer (9.7 hours, P less than 0.05) and total quinidine clearance significantly less (2.64 ml/min per kg, P less than 0.005) than in the young subjects. Renal clearance of quinidine in the elderly was also significantly less (0.99 ml/min per kg, P less than 0.05) than in the young and was associated with lower rates of creatinine clearance in the elderly (r = 0.66). Reduced clearance of quinidine and prolongation of its elimination half-life could predispose to toxicity in the elderly unless the dose were appropriately adjusted.