Circadian changes in procainamide and N-acetylprocainamide kinetics in the rat

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Abstract
The aim of this study was to investigate the possible influence of the time of administration on procainamide and N-acetylprocainamide (NAPA) kinetics in the rat. A single 50 mg kg−1 i.p. dose of procainamide was given to Wistar AF SPF adult male rats maintained under controlled environmental conditions (LD: 06.00h-18.00h) at four different fixed times i.e. 10.00, 16.00, 22.00 and 04.00h. Procainamide and NAPA plasma levels were determined by an immunoenzymatic method. Our data showed significant 24 h variation of the following pharmacokinetic parameters: highest elimination half-lives at l0.00h (t 1/2 β = 0.736 ± 0.020h) for procainamide and at 04.00h (t 1/2 β = 3.55 ± 0.08h) for NAPA (P < 0.001); highest apparent volume of distribution at 04.00h for procainamide (Vd = 2.35 ± 0.17 litre) (P < 0.05); highest ratio AUC NAPA/AUC procainamide at 04.00h (1.039 ± 0.056) (P < 0.001). Procainamide clearance and Cmax and AUC for procainamide and NAPA were not significantly dependent on time of day. These data indicate a 24 h variation in the metabolism of procainamide which is converted to NAPA, the N-acetylation being greatest at 04.00h.

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