RT Journal
A1 Vlasses PH, Kosoglou T, Chase SL, et al
T1 TRimethoprim inhibition of the renal clearance of procainamide and n-acetylprocainamide
JF Archives of Internal Medicine
JO Archives of Internal Medicine
YR 1989
FD June 1
VO 149
IS 6
SP 1350
OP 1353
DO 10.1001/archinte.1989.00390060080016
UL http://dx.doi.org/10.1001/archinte.1989.00390060080016
AB • 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.(Arch Intern Med. 1989;149:1350-1353)