Abstract
The pharmacokinetics of N-acetylprocainamide (NAPA) have been studied in three normal subjects who received 500 mg of this compound by timed intravenous injection. Plasma N APA concentrations and urine excretion were measured by quadrupole mass fragmentography, and a three- compartment pharmacokinetic model was used for data analysis. NAPA elimination half-life and total distribution volume averaged 6.0 hr and 1.38 liters/kg, respectively. Renal excretion of unchanged NAPA accounted for 81% of its elimination, and the mean renal NAPA clearance was 179 ml/min. Approximately 2% of the injected NAPA was deacetylated to procainamide. The fate was not determined of 17% of the NAPA that was estimated to have been eliminated during the 16- hr study period.
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J. Dreyfuss, J. J. Ross, Jr., and E. C. Schreiber. Absorption, excretion and biotransformation of procainamide-C14 in the dog and rhesus monkey.Arzneim. Forsch. 21:948–951 (1971).
J. Dreyfuss, J. T. Bigger, Jr., A. I. Cohn, and E. C. Schreiber. Metabolism of procainamide in rhesus monkey and man.Clin. Pharmacol. Ther. 13:366–371 (1972).
J. Elson, J. M. Strong, W.-K. Lee, and A. J. Atkinson, Jr. Antiarrhythmic potency ofN- acetylprocainamide.Clin. Pharmacol. Ther. 17:134–140 (1975).
E. Karlsson, L. Molin, B. Norlander, and F. Sjöqvist. Acetylation of procaine amide in man studied with a new gas Chromatographie method.Brit. J. Clin. Pharmacol. 1:467–475 (1974).
E. Karlsson, G. Åberg, P. Collste, L. Molin, B. Norlander, and F. Sjöqvist. Acetylation of procainamide in man. A preliminary communication.Eur. J. Clin. Pharmacol. 8:79–81 (1975).
E. E. Bagwell, D. E. Drayer, M. M. Reidenberg, and J. K. Pruett. Effects of theN-acetyl metabolite of procainamide on transmembrane action potentials of canine His Purkinje cells.Clin. Res. 22:676A (1974).
D. E. Drayer, M. M. Reidenberg, and R. W. Sevy. N-Acetylprocainamide: An active metabolite of procainamide.Proc. Soc. Exp. Biol. Med. 146:358–363 (1974).
J. M. Strong and A. J. Atkinson, Jr. Simultaneous measurement of plasma concentrations of lidocaine and its desethylated metabolite by mass fragmentography.Anal. Chem. 44:2287–2290 (1972).
W. P. Deiss and P. P. Cohen. Studies in para-aminohippuric acid synthesis in the human: Its application as a liver function test.J. Clin. Invest. 29:1014–1020 (1950).
C. W. Tabor, M. V. Freeman, J. Baily, and P. K. Smith. Studies on the metabolism of para-aminobenzoic acid.J. Pharmacol. Exp. Ther. 102:98–102 (1951).
M. Berman and M. F. Weiss,SAAM Manual, PHS Publication No. 1073, Government Printing Office, Washington, D.C., 1967.
J. Koch-Weser and S. W. Klein. Procainamide dosage schedules, plasma concentrations, and clinical effects.J. Am. Med. Assoc. 215:1454–1460 (1971).
S. Riegelman, J. Loo, and M. Rowland. Concept of a volume of distribution and possible errors in the evaluation of this parameter.J. Pharm. Sci. 57:128–133 (1968).
T. Teorell. Kinetics of distribution of substances administered to the body. I. The extravascular modes of administration.Arch. Int. Pharmacodyn. 57:205–225 (1937).
D. Perrier and M. Gibaldi. Clearance and biologic half-life as indices of intrinsic hepatic metabolism.J. Pharmacol. Exp. Ther. 191:17–24 (1974).
R. L. Galeazzi, T. Lockwood, L. B. Sheiner, and L. Z. Benet. Urinary excretion of procainamide.Clin. Res. 23:219A (1975).
L. C. Mark, H. J. Kayden, J. M. Steele, J. R. Cooper, I. Berlin, E. A. Rovenstine, and B. B. Brodie. The physiological disposition and cardiac effects of procaine amide.J. Pharmacol. Exp. Ther. 102:5–15 (1951).
A. H. Beckett, J. M. Van Dyk, H. H. Chissick, and J. W. Gorrod. Metabolic oxidation on aliphatic basic nitrogen atoms and their α-carbon atoms-Some unifying principles.J. Pharm. Pharmacol. 23:809–812 (1971).
B. B. Brodie, P. A. Lief, and R. Poet. The fate of procaine in man following its intravenous administration and methods for the estimation of procaine and diethylaminoethanol.J. Pharmacol. Exp. Ther. 94:359–366 (1948).
H. Refsum, K. Frislid, P. K. M. Lunde, and K. H. Landmark. Effects of N-acetylprocamamide as compared with procainamide in isolated rat atria.Eur. J. Pharmacol. (in press, 1975).
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Strong, J.M., Dutcher, J.S., Lee, WK. et al. Pharmacokinetics in man of theN-acetylated metabolite of proeainamide. Journal of Pharmacokinetics and Biopharmaceutics 3, 223–235 (1975). https://doi.org/10.1007/BF01066919
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DOI: https://doi.org/10.1007/BF01066919