In-vitro activity of fleroxacin against isolates causing complicated urinary tract infections and concentrations in seminal and prostatic fluid and in prostatic adenoma tissue.

Fleroxacin is a new fluoroquinolone with a broad antibacterial spectrum and a serum half-life of about 8-12 h. Eighty percent of 400 isolates from complicated or hospital-acquired urinary tract infections were inhibited by a concentration of 1 mg/l and 95% by 4 mg/l. As with other quinolones, fleroxacin is less active in acid urine (pH 5.4) than in Mueller-Hinton broth (pH 7.4). In 12 healthy volunteers the concentrations of fleroxacin were measured in plasma and seminal and prostatic fluid 2, 4 and 12 h after an oral dose of 400 mg. The mean plasma concentrations of three or four volunteers at each time were 4.2, 3.6 and 1.2 mg/l, respectively. The corresponding prostatic fluid/plasma ratios were 0.30, 0.27 and 1.96, respectively. By concomittant administration of ioxitalamic acid it could be demonstrated that in samples obtained 12 h after administration urinary contamination must be considered. Fleroxacin is concentrated in seminal fluid by a median ratio of 1.7. In 13 elderly patients the prostatic fluid and prostatic adenoma tissue concentrations were determined one to four hours following oral administration of 400 mg. The concentrations in prostatic fluid were similar to those of volunteers. The tissue concentrations exceeded plasma concentrations by only about 10% (median). Fleroxacin is very active against isolates causing complicated UTI. Concentrations in seminal and prostatic fluid and prostatic adenoma tissue are sufficiently high to treat bacterial prostatitis or vesiculitis caused by susceptible bacterial strains.

Inhibition of monoamine oxidase by viloxazine in rats.

Biochemical and pharmacological investigations about the effect of the antidepressant drug viloxazine (Vivalan) on catecholamine metabolism in rats led to the following results: Viloxazine exerts a dose and time dependent inhibition of monoamine oxidase activity of brain and liver mitochondrial fraction and tissue homogenates of hypothalamus, heart, liver, and adrenal glands, both in vitro and after oral and parenteral administration in vivo. Consequently, an increase in catecholamine concentrations in brain of rats could be observed after pretreatment with viloxazine. In addition brain serotonin concentrations rose and 5-hydroxy-indoleacetic acid was diminished. However, characterization of inhibition of monoamine oxidase activity by viloxazine in vitro revealed: Compared to the specific inhibitors clorgyline for MAO-A- and pargyline for MAO-B-activity, viloxazine was a very weak inhibitor both for MAO-A and MAO-B in vitro. The type of inhibition was competitive and reversible. From the presented results and the results obtained by other laboratories it is concluded that inhibition of monoamine oxidase activity by viloxazine, although clearly demonstrated in animal experiments, may not be the only mechanism for an antidepressant action of the drug in man.

Pharmacokinetics, in-vitro activity, therapeutic efficacy and clinical safety of aztreonam vs. cefotaxime in the treatment of complicated urinary tract infections.

The minimal inhibitory concentrations (MICs) of aztreonam and cefotaxime were determined against 400 isolates from urological in-patients with complicated and/or hospital acquired urinary tract infections (UTI). Against the Gram-negative rods the activities of both antibiotics were comparable except for higher activity of aztreonam against Pseudomonas aeruginosa. The pharmacokinetic study in nine elderly patients showed a prolonged plasma half life of aztreonam (2.7 h) as compared to younger volunteers (1.6-1.9 h). In a prospective randomized study 39 urological patients with complicated and/or hospital acquired UTI were treated with 1 g aztreonam or cefotaxime iv twice daily for 4 to 15 days. Cure was obtained in 5 out of 18 patients in the aztreonam and 7 out of 20 patients in the cefotaxime group. There were 3 superinfections, 7 relapses and 3 reinfections in the aztreonam group and 1 failure, 1 superinfection, 6 relapses and 5 reinfections in the cefotaxime group. There was no significant difference in therapeutic efficacy between the two antibiotics. Both antibiotics were tolerated well and seem to be equally effective in the treatment of complicated UTI caused by sensitive organisms.

Changes in peripheral and central catecholaminergic and serotoninergic neurons of rats after acute and subacute administration of nicotine.

To establish dose-response relationships for nicotine (acute and subacute administration), we measured hemodynamic parameters as well as circulating and tissue catecholamines in sympathetically innervated organs in rats. We also investigated nicotines's influence on adrenoceptor binding sites of the heart and on serotonin metabolism. In conscious and anesthetized rats, we found a dose-dependent increase in circulating catecholamines after acute injection of nicotine. At low doses nicotine released norepinephrine, resulting in a decrease of blood flow and heart rate, whereas high doses of nicotine released epinephrine, resulting in a reversal of the cardiovascular parameters investigated. In the heart norepinephrine concentration increased after nicotine application. In the lung epinephrine rose markedly, whereas serotonin and 5-hydroxyindolacetic acid were diminished. After subacute administration of nicotine the number of binding sites for 3H-Dihydroalprenolol in the heart was significantly reduced, whereas norepinephrine content was increased. Dopamine, serotonin, and 5-hydroxyindolacetic acid were increased in the hypothalamus. Our findings show that nicotine not only affects peripheral and central catecholaminergic neurons, but also central serotoninergic neurons, thus enhancing turnover of these amines.

Biochemical and morphologic study of catecholamine metabolism in spontaneously hypertensive rats.

Catecholamines and catecholamine-synthesizing enzymes have been studied quantitatively in specific brain areas of spontaneously (genetically) hypertensive rats by means of a combination of sensitive enzymatic-isotopic methods and a microdissecting technique. Changes in catecholamine metabolism were found to be localized to regions of the brain implicated in the regulation of blood pressure. Noradrenaline levels were decreased in specific nuclei of the anterior hypothalamus and in the nucleus interstitialis striae terminalis ventralis. The activity of the adrenaline-forming enzyme, phenyl-ethanolamine-N-methyl transferase, was increased in the A1 and A2 areas of the brain stem. These results implicate catecholamine-forming neurons in the hypothalamus and brain stem in the development of spontaneous hypertension in rats.