A Study of the Potential Interaction Between Bazedoxifene and Atorvastatin in Healthy Postmenopausal Women

Abstract

An open-label, 3-period study was conducted in 30 healthy postmenopausal women (mean age, 58.4 years) who received a single oral dose of atorvastatin 20 mg on day 1 (period 1), multiple daily dosing of bazedoxifene 40 mg on days 4-11 (period 2), and coadministration of atorvastatin 20 mg + bazedoxifene 40 mg on day 12 (period 3). Serial blood samples were collected (24 hours after bazedoxifene and 72 hours after atorvastatin) and assayed for bazedoxifene, atorvastatin, and its ortho-hydroxy and para-hydroxy metabolites. Pharmacokinetic parameters were calculated using noncompartmental methods. Bazedoxifene exposure was not altered with coadministration of atorvastatin 20 mg (C and AUC were within bioequivalence limits). Similarly, atorvastatin and ortho-hydroxyatorvastatin exposure was equivalent with or without coadministration with bazedoxifene. Para-hydroxyatorvastatin concentrations were below the limit of quantitation under both conditions. C for atorvastatin and ortho-hydroxyatorvastatin was 14% and 18% lower, respectively, and T was 20% and 34% longer, respectively, with the combination compared with atorvastatin alone. There were no serious adverse events, and no subjects discontinued the study because of safety. No clinically significant pharmacokinetic interaction was observed between bazedoxifene and atorvastatin or its active metabolites, indicating they may be safely coadministered without dosage adjustment.

Assessment of the Effects of Age and Renal Function on Pharmacokinetics of Bazedoxifene in Postmenopausal Women

“…The pharmacokinetics of BZA have been described in several studies of healthy postmenopausal women . The absolute bioavailability of BZA is approximately 6% .…”

“…The absolute bioavailability of BZA is approximately 6% . The time to maximum plasma concentration (t max ) for BZA 20 to 40 mg is about 1 to 3 hours, reaching a steady state within approximately 7 days . The average half‐life (t ½ ) for BZA is approximately 25 to 30 hours .…”

“…12,13 The pharmacokinetics of BZA have been described in several studies of healthy postmenopausal women. [14][15][16][17] The absolute bioavailability of BZA is approximately 6%. 15 The time to maximum plasma concentration (t max ) for BZA 20 to 40 mg is about 1 to 3 hours, reaching a steady state within approximately 7 days.…”

“…15 The time to maximum plasma concentration (t max ) for BZA 20 to 40 mg is about 1 to 3 hours, reaching a steady state within approximately 7 days. 14,16,17 The average half-life (t ½ ) for BZA is approximately 25 to 30 hours. 14,16 BZA is primarily metabolized via glucuronidation, with little or no metabolism mediated via cytochrome P450 in humans.…”