In Vivo Activity of Intestinal P‐Glycoprotein and Hepatic Organic Anion Transporters Polypeptide in Pregnancy and Postpartum

This study investigates the influence of pregnancy on the in vivo activity of the intestinal P‐glycoprotein (P‐gp) and hepatic organic anion transporters polypeptide (OATP/BCRP) using, respectively, fexofenadine and rosuvastatin as probe drugs. Eleven healthy participants were investigated during the third trimester of pregnancy (Phase 1, 28 to 38 weeks of gestation) and in the postpartum period (Phase 2, 8 to 12 weeks postpartum). In both phases, after administration of a single oral dose of fexofenadine (60 mg) and rosuvastatin (5 mg), serial blood samples were collected for up to 24 h. Rosuvastatin and fexofenadine in plasma were analyzed by LC‐MS/MS using previously validated methods. The pharmacokinetic parameters of fexofenadine and rosuvastatin (Phoenix WinNonLin software) with normal distribution (Shapiro–Wilk test) are presented as geometric mean and 90% confidence interval. Phases 1 and 2 were compared using the t test (P < .05). Fexofexadine AUC0‐24 values do not differ (P‐value: .0715) between Phase 1 (641.9 ng h/mL [500.6‐823.1]) and Phase 2 (823.8 ng h/mL [641.5‐1057.6]) showing that pregnancy (third trimester) does not alter intestinal P‐gp activity. However, rosuvastatin AUC0‐24 values are higher (P‐value: .00005) in Phase 1 (18.7 ng h/mL [13.3‐26.4]) when compared to Phase 2 (9.5 ng h/mL [6.7‐13.4]), suggesting inhibition of OATP1B1/OATP1B3 transporters. In conclusion, pregnancy assessed during the third trimester does not alter the intestinal P‐gp activity but reduces the activity of hepatic OATP1B1/OATP1B3 transporters. Therefore, adjustments in dosage regimens may be necessary for drugs with low therapeutic index, substrates of the OATP1B1/OATP1B3 transporters, administered during the third trimester of pregnancy.