Bazedoxifene Acetate Metabolic Disposition in Healthy, Postmenopausal Women

Abstract

Clinical Pharmacology & Therapeutics (2003) 73, P47–P47; doi:

Conjugated Estrogens and Bazedoxifene

“…1 Serum half-life is 32.8 hours. 24 Administration with a high-fat/high-calorie meal caused no change in bazedoxifene's C max , but it increased the AUC by 25%. No information was provided on how food affected the absorption of conjugated estrogens.…”

“…1 Bazedoxifene is extensively metabolized, with the glucuronidation being the major metabolic pathway. 1,24,25 Bazedoxifene undergoes little or no CYP-450-mediated metabolism. 1,24 Also, bazedoxifene is metabolized by uridine diphosphate glucuronosyltransferase (UGT) in the intestinal tract and liver.…”

Bazedoxifene: A Third-Generation Selective Estrogen Receptor Modulator for Treatment of Postmenopausal Osteoporosis

“…12 The metabolic profile of bazedoxifene was assessed in 6 healthy, postmenopausal women. 13 Blood, urine, and feces were analyzed for radioactivity for 10 days following the administration of a single oral dose of 14 C-bazedoxifene 20 mg. The major route of excretion (84.7%) was via the feces, while only a minor amount (0.81%) of radioactivity was excreted in the urine.…”

Bazedoxifene + conjugated estrogens in HT for the prevention of osteoporosis and treatment of vasomotor symptoms associated with the menopause

“…BZA is extensively metabolized by glucuronidation [21]. The principal uridine diphosphate-glucuronosyl transferase (UGT) isoenzymes involved in the glucuronidation of BZA were UGT1A1, UGT1A8 and UGT1A10, with little or no cytochrome P450 (CYP)-mediated metabolism is observed [21].…”

“…Chandrasekaran et al [21] evaluated the long-term pharmacokinetics of multiple doses of BZA in healthy postmenopausal women (n = 6), a single oral dose of radiolabelled BZA 20 mg, bazedoxifene-5-glucuronide was the major circulating metabolite (40 --95%), while unchanged BZA (£ 13%) and bazedoxifene-4-glucuronide (£ 20%) were present at lower levels. The major route of excretion of radiolabelled BZA was the feces (» 85%); only » 1% of the BZA dose was excreted in the urine.…”