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  • Title: Kinetics of procainamide and N-acetylprocainamide in renal failure.
    Author: Gibson TP, Atkinson AJ, Matusik E, Nelson LD, Briggs WA.
    Journal: Kidney Int; 1977 Dec; 12(6):422-9. PubMed ID: 609192.
    Abstract:
    Four normal subjects and four functionally anephric patients were given 6.5 mg/kg of body wt of procainamide hydrochloride i.v., and plasma concentrations of procainamide (PA) and its major active metabolite N-acetylprocainamide (NAPA) were measured. Two individuals in each group were fast isonicotinic acid hydrazide (INH) and PA acetylators. The pharmacokinetics of PA and NAPA were analyzed with a computer program (SAAM 23). Volume of distribution (Vdss) and renal clearance of PA were similar in normal subjects regardless of acetylator phenotype. Nonrenal clearance was faster (383 vs. 244 ml/min), and PA elimination half-life (t 1/2) was shorter (2.6 vs. 3.5 hr) in fast acetylators. In the functionally anephric patients, Vdss was similar to that of normal subjects. Nonrenal clearence was faster (117.5 vs. 93.5 ml/min) and PA t 1/2 shorter (10.8 vs. 17.0 hr) in fast than in slow acetylators. In these patients, acetylation accounted for 56% of PA elimination, and NAPA concentrations reached 0.8 microgram/ml or more. The t 1/2 of NAPA in renal failure was 41.5 hr, in accord with predictions from studies in normal subjects, assuming no impairment in nonrenal NAPA elimination. PA metabolism, however, is severely impaired by renal failure, so PA t 1/2 was prolonged to an unpredictably greater extent than would be expected from studies in normal subjects.
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