[Nifurpipone disks for antibiograms].
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Biomedical subjects
Publications and source records attributed to I Setnikar.
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A study was made on possible interferences of several drugs on the urinary excretion of nifurpipone and of nitrofurantoin orally administered to rats. Phenobarbital, a microsomial enzyme inducer, SKF 525 A, a microsomial enzyme inhibitor, probenecid, an inhibitor of the tubular acid secretory system, quanine, an inhibitor of the tubular alkaline secretory system, and hydrochlorothiazide, a diuretic, were studied. None of these treatments altered in an important way the urinary excretion of nifurpipone or of nitrofurantoin.
The protein binding properties of piperidino-3-methylflavone-8-carboxylate (flavoxate, F) and of its main metabolite, i.e. 3-methylflavone-8-carboxylic acid (M), were investigated by dialysis-equilibrium technique. During the dialysis, F hydrolyzes to a notable extent into M. Therefore a true equilibrium of F could not be obtained. With this limitation, the results show that F has a small protein affinity. The protein binding properties of M were separately investigated with bovine albumin, human albumin and with human, rat, rabbit and dog plasma. The Freundlich's isotherms, which describe the affinities of albumin to M, were calculated. They show that unconjugated M, possibly present in plasma, is by 99.5% in a protein-bound form.
The plasma levels, the urinary excretion and the biliary excretion of piperidinoethyl-3-methylflavone-8-carboxylate (flavoxate, F) were studied in rats after i.v. and after oral administration. Parallel experiments were made with 3-methyl-flavone-8-carboxylic acid (M), the main metabolite of F. The substances are found in blood and are excreted in the urine and in the bile. The quantities excreted in the urine after oral administration are similar to those excreted after i.v. administration, showing that the enteric availability of the drugs is almost complete. The end product in urine and in bile is represented by a substance which yields M after a strong acid hydrolysis. There are marked pharmacokinetic differences between F and M, probably related to their physical properties.
The c-AMP phosphodiesterase inhibiting properties of flavoxate and of its main metabolite i.e. 3-methylflavone-8-carboxylic acid (MFCA), were assayed in vitro and compared to those of theophylline. Flavoxate and MFCA are competitive phosphodiesterase inhibitors, and are 21 and respectively 5 times more potent than theophylline. The smooth muscle relaxing activity of flavoxate possibly relies on this enzymatic mechanism.
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