title: Pharmacokinetics of N-acetylprocainamide in patients profiled with a stable isotope method.
abstract: 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.
authors: Department of Medicine, Northwestern University Medical School, Chicago, IL 60611.
authors: A J
authors: AJ
authors: Atkinson
authors: T I
authors: TI
authors: Ruo
authors: A A
authors: AA
authors: Piergies
authors: H C
authors: HC
authors: Breiter
authors: T J
authors: TJ
authors: Connelly
authors: G S
authors: GS
authors: Sedek
authors: D
authors: D
authors: Juan
authors: G L
authors: GL
authors: Hubler
authors: A M
authors: AM
authors: Hsieh
mesh_terms: D000042:Absorption; D000120:Acecainide / Q000493:pharmacokinetics*; D000368:Aged; D002247:Carbon Isotopes; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011342:Procainamide / Q000031:analogs & derivatives*
chemical_list: D002247:Carbon Isotopes; D000120:Acecainide; D011342:Procainamide