The antiarrhythmic efficacy and safety of oral flecainide acetate were assessed during a controlled, short-term dosage-maintenance study. Thirteen patients with chronic ventricular ectopy entered a placebo control period, and 11 with persistent, frequent (greater than 600 per 12 hours) premature ventricular complexes (PVCs) advanced to drug therapy. Of 10 patients completing a trial of different doses, nine responded completely, with a mean PVC suppression of 98,3 per cent. Repetitive PVCs were eliminated. The mean effective dose was 189 mg per 12 hours, and the effective plasma concentration before administration of a dose averaged 635 ng per milliliter. One patient responded partially (68 per cent of PVCs suppressed). Flecainide continued to be effective and well tolerated at the end of a two-week outpatient trial in the nine complete responders, maintaining an average PVC suppression of 94.6 per cent. The PR and QRS intervals were mildly prolonged. The echocardiographic ejection fraction was unchanged during treatment. The elimination half-life was long - 18.8 +/- 3.8 hours. Flecainide thus appears to be a highly effective and well-tolerated antiarrhythmic agent with favorable pharmacokinetics.

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The antimicrobial activity of flumequine (R-802) was characterized by in vitro and in vivo procedures. Assay of the minimal inhibitory concentrations for 321 recent clinical isolates revealed that 88% of the gram-negative bacteria were inhibited by an R-802 concentration of 6.2 ,ug/ml or less. Cross-resistance in laboratory-derived mutants ofProteus vulgaris was essentially complete for R-802, nalidixic acid, and oxolinic acid, although quantitative differences were evident. R-802 was more effective than either of these quinolone antibacterials in preventing the development of experimental murine pyelonephritis (P. vulgaris). R-802 and trimethoprim/sulfamethoxazole (1:5) were equally effective in resolving a P. mirabilis-induced prostatitis of rats.Flumequine (R-802) is a synthetic antibacterial, selected from a series of tricyclic quinolines prepared in Riker Laboratories. The compound is 6,7-dihydro-9-fluoro-5-methyl-1-oxo-1H,5H (U) quinolizine-2-carboxylic acid (Fig. 1) Antimicrobials. Flumequine (R-802) was synthesized in Riker Research Laboratories. Stock solutions of R-802 (1%) for in vitro use were prepared with 0.1 N sodium hydroxide. Nalidixic acid and oxolinic acid were provided by Winthrop Laboratories and Warner-Lambert Research Institute, respectively. Bactrim (sulfamethoxazole and trimethoprim, 5:1), Erythrocin (erythromycin stearate), and Terramycin (oxytetracyline-hydrochloride) were obtained in commercial form.Susceptibility. The antimicrobial spectrum of R-802 was surveyed on tryptone soy agar (TSA) plates with a log,0 dilution series. Microliter aliquots of stock solution were mixed with molten TSA in individual screw-cap vials and dispensed into petri dishes. These preparations were allowed to harden and were surface inoculated with stock culture suspensions. The conditions of incubation were overnight at 37 C in a humidified atmosphere enriched with 10% carbon dioxide. Growth inhibition of those strains that appeared to be most susceptible to R-802 was further examined by a log2 dilution tube technique in nutrient broth (5). Nalidixic acid and oxolinic acid were included in this titration as reference quinolone antibacterials. Bacillus subtilis was deleted in this comparison because of pellicle formation in static broth culture; Proteus vulgaris, which was not tested on TSA because of the "swarming" phenomenon, was included here. The minimal inhibitory concentrations (MICs) of R-802 for clinical isolates of urinary tract infection were similarly determined; the influence ofculture medium pH was examined in selected strains at 0.2-unit intervals over the range 6.0 to 8.0.Cross-resistance of mutant clones selected by growth on oxolinic acid, nalidixic acid, and R-802 was assessed by the replica plating technique (6). Approximately 109 cells were spread over the surface of drug plates containing TSA plus 0.15% bile salts to inhibit swarming ofP. vulgaris 210. The levels of drug permitting development of approximately 10 colonies/plate were as follows: R-802 and oxolinic acid, 10 ,ig/ml; nalidix...

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