Pharmacokinetic Drug Interaction Study of Bazedoxifene and Ibuprofen

Abstract

The purpose of this article was to evaluate the potential for a pharmacokinetic interaction between bazedoxifene and ibuprofen. In a randomized crossover study, 12 healthy postmenopausal women (aged 45-65 years) received either a single oral dose of ibuprofen (600-mg tablet), bazedoxifene (20-mg capsule), or both ibuprofen and bazedoxifene during the 3 treatment periods. Serial blood samples were collected for pharmacokinetic analyses. There was no relationship between the UGT1A1 genotype and bazedoxifene clearance. The 90% log-transformed confidence intervals (CIs) for bazedoxifene C , 96% to 144%, and AUC, 85% to 134%, were slightly above the bioequivalence limits of 80% to 125%. The 90% log-transformed CIs for ibuprofen pharmacokinetic parameters were within these limits (C , 92%-122%; AUC, 94%-106%). The increase in bazedoxifene plasma concentrations when combined with ibuprofen versus bazedoxifene alone is unlikely to be clinically significant. The lack of interaction between bazedoxifene and ibuprofen suggests that they may be coadministered without dose 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.…”

“…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. 18,19 The major route of excretion for BZA was found to be via the feces (85%), with less than 1% excreted in the urine.…”