Tamoxifen Therapy Is Associated With Altered Intestinal P-Glycoprotein Activity In Vivo

Area of Science:

• Pharmacology
• Drug Metabolism and Transporter Studies

Background:

• Tamoxifen (TAM) is known to interact with P-glycoprotein (P-gp) in preclinical models.
• Its impact on intestinal P-gp activity in humans in vivo is not well understood.

Purpose of the Study:

• To investigate the effect of tamoxifen therapy on intestinal P-glycoprotein (P-gp) activity in women.
• To evaluate P-gp mediated drug disposition using fexofenadine (FEXO) as a probe substrate.

Main Methods:

• A pharmacokinetic study involving 16 women on tamoxifen and 12 healthy controls.
• Administration of a single oral dose of fexofenadine (120 mg) to all participants.
• Quantification of plasma fexofenadine concentrations over 12 hours using LC-MS/MS.

Main Results:

• Systemic exposure (AUC0-12h and AUC0-∞) to fexofenadine was significantly lower in women receiving tamoxifen.
• Apparent oral clearance (CL/F) of fexofenadine was higher in the tamoxifen group.
• Elimination half-life of fexofenadine remained unchanged between groups.

Conclusions:

• Tamoxifen therapy appears to modulate intestinal P-gp activity, leading to reduced oral bioavailability of probe substrate fexofenadine.
• These findings suggest potential drug interactions with co-administered oral P-gp substrates.
• Further clinical pharmacology studies are warranted to confirm these implications.