Metabonomic evaluation of idiosyncrasy-like liver injury in rats cotreated with ranitidine and lipopolysaccharide.

Idiosyncratic liver injury occurs in a small fraction of people on certain drug regimens. The cause of idiosyncratic hepatotoxicity is not known; however, it has been proposed that environmental factors such as concurrent inflammation initiated by bacterial lipopolysaccharide (LPS) increase an individual's susceptibility to drug toxicity. Ranitidine (RAN), a histamine-2 receptor antagonist, causes idiosyncratic liver injury in humans.

Pharmacokinetics and metabolism of [14C]eplerenone after oral administration to humans.

A pharmacokinetics and metabolism study was conducted in eight healthy human volunteers. After oral administration of [14C]eplerenone (EP) at a dose of 100 mg per person as an aqueous solution, blood, saliva, breath, urine, and fecal samples were collected at various time points. All matrices were analyzed for total radioactivity and/or for EP and its open-lactone-ring form (EPA).

Contemporary issues in toxicology the role of metabonomics in toxicology and its evaluation by the COMET project.

The role that metabonomics has in the evaluation of xenobiotic toxicity studies is presented here together with a brief summary of published studies. To provide a comprehensive assessment of this approach, the Consortium for Metabonomic Toxicology (COMET) has been formed between six pharmaceutical companies and Imperial College of Science, Technology and Medicine (IC), London, UK. The objective of this group is to define methodologies and to apply metabonomic data generated using (1)H NMR spectroscopy of urine and blood serum for preclinical toxicological screening of candidate drugs.

Pharmacokinetics and metabolism of a COX-2 inhibitor, valdecoxib, in mice.

The pharmacokinetics and metabolism of valdecoxib, a potent cyclooxygenase-2 selective inhibitor, were investigated in mice. Valdecoxib was extensively metabolized after a single 5 mg/kg oral administration of [(14)C]valdecoxib and elimination of unchanged drug was minor (less than 1%) in male and female mice. The total mean percentage of administered radioactive dose recovered was 99.

Disposition of a specific cyclooxygenase-2 inhibitor, valdecoxib, in human.

Valdecoxib is a potent and specific inhibitor of cyclooxygenase-2, which is used for the treatment of rheumatoid arthritis, osteoarthritis, and the dysmenorrhea pain. Eight male human subjects each received a single 50-mg oral dose of [(14)C]valdecoxib. Urine, feces, and blood samples were collected after administration of the radioactive dose.