Isolation and structural elucidation of biotransformation products from acarbose.

Following oral administration the a-glucosidase inhibitor acarbose (O-4,6-dideoxy-4-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl) -2-cyclohexen-1-yl]amino]-a-D-glucopyranosyl-(1----4)-O-a-D-glu copyranosyl-(1----4)-D-glucopyranose, Bay g 5421) is degraded by digestive enzymes and/or intestinal microorganism. The effect of anaerobic intestinal bacteria can be studied in an in vitro model which involves the incubation of acarbose with human or animal intestinal flora. Acarbose and nine biotransformation products can be isolated from the incubation mixture.

Pharmacokinetics of acarbose. Part I: Absorption, concentration in plasma, metabolism and excretion after single administration of [14C]acarbose to rats, dogs and man.

The absorption, disposition, metabolism, and excretion of acarbose (O-4,6-dideoxy-4-[[(1S, 4R, 5S, 6S)-4,5,6-trihydroxy-3- (hydroxymethyl)-2- cyclohexen-1-yl]amino]-a-D-glucopyranosyl- (1----4)-O-a-D-glucopyranosyl- (1----4) -D-glucopyranose, Bay g 5421) have been studied following a single administration of the 14C-labelled compound to rats and dogs via different routes (intravenous, oral, intraduodenal) in the dose range of 2-200 mg.kg-1 as well as to man in a single oral dose of 200 mg. After intravenous administration [14C]acarbose was eliminated rapidly and completely via the renal route.

Antibacterial activity of the metabolites of ciprofloxacin and its significance in the bioassay.

The antibacterial activity of the metabolites of ciprofloxacin (1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3- quinolinecarboxylic acid, Bay o 9867; designated tradename: Ciprobay) M1, M2, M3 and M4 was tested with the agar dilution method against various Gram-positive and Gram-negative bacteria in comparison to ciprofloxacin, norfloxacin and nalidixic acid. The results show that M1 had only a weak antibacterial activity comparable to nalidixic acid, whereas M2 was significantly less active. M3, which is one of the main metabolites in urine has a broad antibacterial activity but was less active than ciprofloxacin or norfloxacin.

Isolation and structural elucidation of urinary metabolites of ciprofloxacin.

After oral administration of 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-piperazine-1-ylquinoline++ +-3-carboxylic acid (ciprofloxacin, Bay o 9867; designated trademark: Ciprobay) four metabolites M1-M4 were isolated from human urine by Craig counter current distribution and semipreparative high-performance liquid chromatography. Their molecular structures were elucidated by nuclear magnetic resonance and mass spectrometry and confirmed by comparing their spectra with those of authentic synthetic reference compounds.

A high performance liquid chromatographic method for the determination of kinin releasing activity of kallikrein.

An HPLC method for measuring the in vitro kinin-forming activity of Kallikrein (K), is described. Kinins are formed by incubating K with partially purified bovine kininogen. An aliquot portion of the incubation solution is injected directly onto the chromatographic column (RP-18, 10 um, length 25 cm, 4 mm i.