Trimethoprim inhibition of the renal clearance of procainamide and N-acetylprocainamide.
To test the effect of trimethoprim (an antibiotic commonly administered with sulfamethoxazole) on the disposition of the antiarrhythmic procainamide hydrochloride and its active metabolite N-acetylprocainamide, 10 healthy men received 1 g of procainamide hydrochloride orally on two occasions, coadministered with placebo or trimethoprim (100 mg twice a day for 2 days before and then 200 mg with the procainamide dose). Trimethoprim decreased the mean (+/- SD) renal clearance by 45% after the dose of procainamide was administered (487 +/- 129 vs 267 +/- 123 mL/min) and that of N-acetylprocainamide by 26% (275 +/- 78 vs 192 +/- 82 mL/min) compared with placebo. The mean area under plasma concentration--time curve 0 to 12 hours after dosing increased 39% for procainamide (19.8 +/- 4.8 vs 27.6 +/- 7.2 mg.h/L) and 27% for N-acetylprocainamide (9.1 +/- 2.1 vs 11.4 +/- 2.8 mg.h/L). The corrected QT electrocardiographic interval at 2 hours after the procainamide dose was 0.40 +/- 0.02 second with placebo and 0.43 +/- 0.03 second with trimethoprim. Trimethoprim may increase procainamide and N-acetylprocainamide plasma concentrations, resulting in increased pharmacodynamic response apparently caused by the competition for renal tubular cationic secretion.
Vlasses
P H
PH
Division of Clinical Pharmacology, Jefferson Medical College, Philadelphia, PA 19107.
Kosoglou
T
T
Chase
S L
SL
Greenspon
A J
AJ
Lottes
S
S
Andress
E
E
Ferguson
R K
RK
Rocci
M L
ML
D000120:Acecainide / Q000493:pharmacokinetics*; D000328:Adult; D004347:Drug Interactions; D004562:Electrocardiography; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D011342:Procainamide / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D011897:Random Allocation; D012016:Reference Values; D014295:Trimethoprim / Q000494:pharmacology*
D000120:Acecainide; D014295:Trimethoprim; D011342:Procainamide