Disposition and metabolism of tenidap in the rat.

Tenidap is a new antirheumatic drug currently undergoing clinical evaluation. It inhibits production and activity of cytokines in vivo and causes significant reductions in plasma markers of disease activity in rheumatoid arthritis. After the oral administration of C-14 labeled tenidap, bile, urine and plasma were examined by HPLC and atmospheric pressure tandem mass spectrometry.

Sertraline. Chronopharmacokinetics and the effect of coadministration with food.

Two nonblinded single-dose randomised 3-way crossover studies were conducted in healthy male volunteers to determine the effect of the time of administration (morning vs evening) and the effect of food on the pharmacokinetics of sertraline tablets. There were no significant treatment effects on the mean area under the plasma concentration-time curve (AUC), mean peak plasma sertraline concentration (Cmax), mean time to reach Cmax (tmax), mean terminal elimination half-life, or the mean elimination rate constant in either study. The results of these 2 studies show that the bioavailability and elimination of sertraline tablets are not influenced by the time of administration or administration with or without food.

Pharmacokinetics of sertraline and its N-demethyl metabolite in elderly and young male and female volunteers.

A nonblinded study was conducted to compare the pharmacokinetic properties of the selective serotonin reuptake inhibitor sertraline in 22 young (aged 18 to 45 years) and 22 elderly (> 65 years) volunteers, of whom half were male and half were female. In this study, sertraline was administered at a dosage of 200mg once daily (the maximum recommended daily dosage) for 21 days after upward dosage titration from 50 mg/day over a 9-day period. Thus, this study was designed to measure the effect of age and gender on the pharmacokinetic properties of sertraline at the maximum dosage recommended for clinical use.

The Effect of Urinary pH and Flow Rate on the Renal Elimination of Zopolrestat and Zopolrestat Glucuronide in Humans.

Zopolrestat is an aldose reductase inhibitor that may be useful in the treatment of diabetic complications by reducing flux through the polyol pathway. The plasma half-life of zopolrestat in man is approximately 30 h, and approximately 45% of an orally administered 1000-mg dose is eliminated in the urine as unchanged drug. Because active secretion accounts for much of the renal clearance for zopolrestat, a carboxylic acid with a pK(a) of 5.

Pharmacokinetics of the aldose reductase inhibitor, zopolrestat, in humans.

The pharmacokinetics of zopolrestat, an aldose reductase inhibitor that may be useful for the treatment of complications of diabetes, have been investigated using oral doses ranging from 50 to 1200 mg administered to healthy male volunteers. In a single-dose study, Cmax, AUC(0-48), and urinary elimination of zopolrestat increased linearly with increasing dose. The amount of zopolrestat excreted unchanged in the urine within 48 hours ranged from 34 to 45% of the administered dose.