Intestinal P-gp activity is reduced in postmenopausal women under breast cancer therapy.

Intestinal P-glycoprotein (P-gp) activity plays a crucial role in modulating the oral bioavailability of its substrates. Fexofenadine has commonly been employed as a P-gp probe, although it's important to note the involvement of other drug transporters like OATP1B1, OATP1B3, and OATP2B1. In vitro studies demonstrated an upregulation of P-gp protein in response to exposure to pregnancy-related hormones. The objective of this study was to investigate how intestinal P-gp activity is impacted by menopausal status. This study sampled fexofenadine plasma concentrations over 0-4h after probe drug administration from two groups of breast cancer patients: pre-menopausal (n=20) and post-menopausal (n=20). Fexofenadine plasma concentrations were quantified using LC-MS/MS. AUCinf was calculated through limited sampling strategies equation. Multiple linear regression was applied on AUCinf , Cmax, and Tmax. Post-menopausal patients showed a significant increase in Cmax (geometric mean and CI 95%) [143.54 (110.95-176.13) vs 223.54 ng/mL (161.02-286.06)] and in AUCinf [685.55 (534.98-878.50) vs 933.54 ng·h/mL (735.45-1184.99)] compared to pre-menopausal patients. The carriers of the ABCB1 3435 allele T displayed higher Cmax values of 166.59 (CI 95% 129.44 - 214.39) compared to the wild type at 147.47 ng/mL (CI 95% 111.91 - 194.34) (p = 0.02). In postmenopausal individuals, the decrease in P-gp activity of approximately 40% may lead to an increased plasma exposure of orally administered P-gp substrates.