The effect of flecainide acetate, a new antiarrhythmic, on plasma digoxin levels.

The possible effect of oral flecainide acetate on steady-state digoxin levels was assessed in 15 healthy men. Each volunteer received digoxin 0.25 mg daily (8 AM) for 22 consecutive days and flecainide 200 mg bid (8 AM and 8 PM) on days 11 through 15. Plasma digoxin and flecainide levels were measured by radioimmunoassay and gas-liquid chromatography methods, respectively. Flecainide levels were within the range associated with suppression of premature ventricular contractions in patients. Mean plasma digoxin levels just before the 8 AM dose were 0.46 ng/mL on days 9 and 10 (baseline), 0.57 ng/mL (P less than .05) on day 13, and 0.49 ng/mL (not significant [NS]) on day 15. Compared with a mean six-hour postdose baseline digoxin level of 0.58 ng/mL, postdose levels were 0.62 ng/mL (NS) and 0.65 ng/mL (P less than .05) on days 13 and 15, respectively. On an average for each subject, predose and six-hour postdose digoxin levels increased by 24 +/- 35% and 13 +/- 19%, respectively, during coadministration. The changes in electrocardiographic intervals and vital signs that occurred during concomitant drug administration were not clinically significant although a slight prolongation of the PR interval was noted in some subjects. Unless plasma digoxin levels are in the upper end of the therapeutic range, changes in magnitude as observed in this study should be clinically inconsequential for most patients.

Effect of ten new beta-lactam antibiotics on urine glucose test methods.

The effect of ten new beta-lactam antibiotics (cefoperazone, cefotaxime and its metabolite desacetylcefotaxime, ceftazidime, ceftizoxime, ceftriaxone, aztreonam, azlocillin, mezlocillin, piperacillin, and ticarcillin) on the accuracy of Clinitest, Diastix, and Tes Tape determinations of glycosuria was investigated. Solutions of each of the antibiotics were prepared in urine over a range of clinically obtainable drug concentrations. Urine samples from a healthy subject were used to prepare simulated diabetic urine by adding dextrose to achieve concentrations of 0.5%, 1%, and 2%. With penicillin derivatives, falsely elevated Clinitest readings generally were observed at lower glucose concentrations. When no glucose was present, cephalosporins and the monobactam, aztreonam, gave a dark green-black color that could only be interpreted as 0% on the Clinitest color chart. At higher urine glucose concentrations (1% and 2%), no interaction with Clinitest could be demonstrated, with the exception of a few falsely reduced readings. All urine solutions containing beta-lactam antibiotics were estimated accurately by both Diastix and Tes Tape. The unpredictability of the Clinitest-beta-lactam antibiotics interaction should discourage the use of this urine glucose test in patients who receive these drugs. The glucose-oxidase tests, Diastix and Tes Tape, may be used as qualitative tests for glycosuria in patients treated with beta-lactam antibiotics.

Lack of interference of five new beta-lactam antibiotics with serum creatinine determination.

Several cephalosporins falsely elevate creatinine concentration as determined by the Jaffé reaction. We studied the in vitro effect of various concentrations of cefoperazone, ceftizoxime, ceftriaxone, ceftazidime, and azthreonam on the creatinine determination in serum, using both a manual and an automated technique. No false elevation or change in baseline creatinine concentration could be observed with any of the five antibiotics. With the use of large concentrations in serum of these beta-lactam antibiotics, we can estimate their lack of interference with creatinine determination in urine as well. Therefore, there is no need to relate the timing of blood (and urine) sampling for creatinine assay to dosage of these antibiotics.

Effect of probenecid on the pharmacokinetics of ceftizoxime.

The effect of probenecid on the pharmacokinetics of ceftizoxime was studied. Twelve healthy male volunteers first received 1 g of ceftizoxime either by iv rapid injection or by im injection. One week later, each subject was again given a similar dose of ceftizoxime, one hour after the ingestion of 1 g of probenecid. Serum and urinary concentrations were determined by a HPLC method. Ceftizoxime half-life was increased by probenecid from 1.7 to 2.3 h in the iv group, and 1.9 to 2.8 h in the im group (P less than 0.05, paired t-test). Probenecid increased the area under the serum concentration-time curve by 49% in both groups. There was no significant change in the volume of distribution following probenecid. This study confirms that ceftizoxime is eliminated by glomerular filtration and tubular secretion and that the latter is inhibited by probenecid.