Preparation of the glucosylamines of procainamide and evaluation of the pharmacokinetics of the beta-glucosylamine of procainamide in the conscious rabbit

An aqueous solution of the glucosylamines formed when procainamide reacts with glucose has been prepared and the kinetics of the elimination of the beta-anomer has been investigated in the conscious rabbit. Analytical methods were developed for the beta-ducosylamine and for both procainamide and N-acetylprocainamide. The beta-glucosylamine was not converted to procainamide in vivo and showed monoexponential elimination kinetics with a mean (+/- 1 S.D.) t(1/2) of 0.92 +/- 0.11 h and a V-z of 0.16 +/- 0.03 1/kg as opposed to 0.93 +/- 0.10 h and 6.09 +/- 1.17 1/kg, respectively for procainamide. Simulations using this data indicated that administration of an infusion of procainamide hydrochloride in 5% glucose to human subjects could result in steady-state plasma concentrations of the beta-glucosylamine which are fifteen times greater than for procainamide. The biological activity of the glucosylamines of procainamide remains to be studied. (C) 1997 Elsevier Science B.V.