Isolation and characterization of cetirizine degradation product: mechanism of cetirizine oxidation.

Purpose: The goal of the study was to isolate and analyze a cetirizine degradation product, formed within a PEG-containing formulation and to elucidate the mechanism of oxidation of cetirizine.

Methods: Cetirizine, formulated in PEG-containing matrix, was subjected to forced degradation conditions in the pH range from 3 to 10, and the product was analyzed by HPLC and LC-MS/MS. Additionally, pure cetirizine was subjected to selective oxidization by hydrogen peroxide and sodium percarbonate.

Bioequivalence studies of a new valproic acid delayed-release capsule and divalproex sodium delayed-release tablet.

Objective: The study examined relative bioavailability of a novel valproic acid (VPA) delayed-release (DR) soft gelatin capsule formulation to divalproex sodium DR tablet under fasting conditions and the effect of food on the bioavailability of the VPA DR soft gelatin capsule.

Method: This open-label, randomized three-way crossover study enrolled 36 healthy non-smoking adult volunteers. Treatments included a single 500 mg divalproex sodium DR tablet, fasting; a single 500 mg VPA DR soft gelatin capsule, fasting; and, a single 500 mg VPA DR soft gelatin capsule 500 mg, non-fasting.

Identification of phenylisoxazolines as novel and viable antibacterial agents active against Gram-positive pathogens.

A new and promising group of antibacterial agents, collectively known as the oxazolidinones and exemplified by linezolid (PNU-100766, marketed as Zyvox), have recently emerged as important new therapeutic agents for the treatment of infections caused by Gram-positive bacteria. Because of their significance, extensive synthetic investigations into the structure-activity relationships of the oxazolidinones have been conducted at Pharmacia. One facet of this research effort has focused on the identification of bioisosteric replacements for the usual oxazolidinone A-ring.

Identification of a novel oxazolidinone (U-100480) with potent antimycobacterial activity.

During the course of our investigations in the oxazolidinone antibacterial agent area, we have identified a subclass with especially potent in vitro activity against mycobacteria. The salient structural feature of these oxazolidinone analogues, 6 (U-100480), 7 (U-101603), and 8 (U-101244), is their appended thiomorpholine moiety. The rational design, synthesis, and evaluation of the in vitro antimycobacterial activity of these analogues is described.