Pharmacokinetics of N-acetylprocainamide in patients profiled with a stable isotope method

N-Acetylprocainamide (NAPA) absorption and disposition were profiled in five patients with ventricular arrhythmias by the simultaneous intravenous administration of NAPA-¹³C and oral administration of a 500 mg NAPA hydrochloride tablet. NAPA distribution was modeled with a three compartment mammillary system. The central compartment volume of 14.1 ± 2.6 L (mean ± SD) was similar to expected intravascular space, corrected for NAPA partitioning between erythrocytes and plasma. Other compartment volumes, intercompartmental and nonrenal clearances, and the steady-state distribution volume of 1.45 ± 0.09 L/kg were similar to normal subject values. The least-squares estimate of 1.67 for the NAPA renal clearance/creatinine clearance ratio was similar to the value of 1.68 previously reported for functionally anephric patients and showed the expected age-associated decrease. The oral NAPA dose was 78.0% ± 11.7% absorbed and interindividual variation in NAPA absorption was correlated with fast intercompartmental clearance (r = 0.89, p = 0.045). Because fast intercompartmental clearance partly reflects splanchnic blood flow, hemodynamic changes may affect NAPA bioavailability, as has been found for procainamide.