Ranitidine-induced changes in the renal and hepatic clearances of procainamide are correlated.
Ranitidine, procainamide and its active N-acetyl metabolite (NAPA) are renally secreted bases which can compete for carrier-mediated transport processes. The effect of ranitidine on the disposition of procainamide and NAPA was evaluated in 13 healthy men. Subjects were randomized to receive p.o. procainamide (1000 mg) alone (base line) and after p.o. ranitidine, 150 mg twice a day for 4 days. Blood and urine samples were collected at frequent intervals for 24 hr after the procainamide dose. There were no significant differences in the mean pharmacokinetic parameters of procainamide and NAPA after ranitidine coadministration compared to base line. However, individual changes did occur and regression analysis revealed a correlation between base-line procainamide renal clearance (CLR) and the change (delta) in CLR after ranitidine (r = 0.69, P less than .01). Subsequently, individuals were separated into Group I (n = 7) if they had a decrease or Group II (n = 6) if they had an increase in procainamide CLR after ranitidine. Mean +/- S.D. base-line procainamide CLR was 539 +/- 114 ml/min for Group I vs. 410 +/- 61 ml/min for Group II (P less than .01). During ranitidine coadministration, Group I had a 23% decrease in mean procainamide CLR (P less than .05), whereas Group II had a 21% increase (P less than .05). There were no significant differences in the metabolic clearance (CLM) of procainamide between the two groups at base line. However, Group I had a 45% increase (P less than .01) whereas Group II had a 41% decrease (P less than .05) in mean procainamide CLM with concomitant ranitidine.(ABSTRACT TRUNCATED AT 250 WORDS)
Rocci
M L
ML
Division of Clinical Pharmacology, Jefferson Medical College, Philadelphia, Pennsylvania.
Kosoglou
T
T
Ferguson
R K
RK
Vlasses
P H
PH
D000120:Acecainide / Q000493:pharmacokinetics; D000328:Adult; D004347:Drug Interactions; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D011342:Procainamide / Q000493:pharmacokinetics*; D011899:Ranitidine / Q000494:pharmacology*
D011899:Ranitidine; D000120:Acecainide; D011342:Procainamide