Disposition of bazedoxifene in rats.

Bazedoxifene acetate (BZA), a novel selective estrogen receptor modulator, is currently being developed for the prevention and treatment of osteoporosis in post-menopausal women. In this study, the disposition of BZA was determined in the rat, a pharmacology and safety model. After a single 0.

In vitro metabolism, permeability, and efflux of bazedoxifene in humans.

Bazedoxifene (BZA) acetate, a novel estrogen receptor modulator being developed for the prevention and treatment of postmenopausal osteoporosis, undergoes extensive metabolism in women after oral administration. In this study, the in vitro metabolism of [(14)C]BZA was determined in human hepatocytes and hepatic and intestinal microsomes, and the UDP glucuronosyltransferase (UGT) isozymes involved in the glucuronidation of BZA were identified. In addition, BZA was evaluated for its potential as a substrate of P-glycoprotein (P-gp) transporter in Caco-2 cell monolayers.

In vitro metabolism and identification of human enzymes involved in the metabolism of methylnaltrexone.

Methylnaltrexone (MNTX) is a peripherally acting mu-opioid receptor antagonist and is currently indicated for the treatment of opioid-induced constipation in patients with advanced illness who are receiving palliative care, when response to laxative therapy has not been sufficient. Sulfation to MNTX-3-sulfate (M2) and carbonyl reduction to methyl-6alpha-naltrexol (M4) and methyl-6beta-naltrexol (M5) are the primary metabolic pathways for MNTX in humans. The objectives of this study were to investigate MNTX in vitro metabolism in human and nonclinical species and to identify the human enzymes involved in MNTX metabolism.

Metabolism of intravenous methylnaltrexone in mice, rats, dogs, and humans.

Methylnaltrexone (MNTX), a selective mu-opioid receptor antagonist, functions as a peripherally acting receptor antagonist in tissues of the gastrointestinal tract. This report describes the metabolic fate of [(3)H]MNTX or [(14)C]MNTX bromide in mice, rats, dogs, and humans after intravenous administration. Separation and identification of plasma and urinary MNTX metabolites was achieved by high-performance liquid chromatography-radioactivity detection and liquid chromatography/mass spectrometry.

Species differences in the formation of vabicaserin carbamoyl glucuronide.

Vabicaserin is a potent 5-hydroxtryptamine 2C full agonist with therapeutic potential for a wide array of psychiatric disorders. Metabolite profiles indicated that vabicaserin was extensively metabolized via carbamoyl glucuronidation after oral administration in humans. In the present study, the differences in the extent of vabicaserin carbamoyl glucuronide (CG) formation in humans and in animals used for safety assessment were investigated.