TITLE

Kinetics of procainamide and N-acetylprocainamide in renal failure

AUTHOR(S)
Gibson, Thomas P.; Atkinson, Jr., Arthur J.; Matusik, Edward; Nelson, Lee D.; Briggs, William A.
PUB. DATE
December 1977
SOURCE
Kidney International;Dec1977, Vol. 12 Issue 6, p422
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
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 (t½) 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 clearance was faster (117.5 vs. 93.5 ml/min) and PA t½ 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 μg/ml or more. The t½ 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 t½ was prolonged to an unpredictably greater extent than would be expected from studies in normal subjects.
ACCESSION #
17680861

 

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