This study evaluates the influence of pregnancy and HIV infection in conjunction with the use of raltegravir, lamivudine, and tenofovir disoproxil fumarate (combined antiretroviral therapy [cART]) on intestinal P-glycoprotein (P-gp) and hepatic organic anion transporter polypeptide (OATP) 1B1/1B3 and/or breast cancer resistance protein (BCRP) drug transporter activity using rosuvastatin (OATP1B/BCRP) and fexofenadine (P-gp) probes. Single oral doses of 5-mg rosuvastatin and 60-mg fexofenadine were administered to women living with HIV under cART in the third trimester of gestation (n = 15) and postpartum period (n = 10). A control group of 12 healthy nonpregnant women also was investigated. Pharmacokinetic parameters were estimated by using a noncompartmental method and evaluated by t test (P < .05). The rosuvastatin area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUC0-last ) value was higher in the third trimester of pregnancy (19.5 [95%CI, 16.8-22.3] ng • h/mL] when compared to postpartum (13.3 [95%CI, 9.3-17.5] ng • h/mL), while the fexofenadine AUC0-last values did not differ between the third trimester of pregnancy (738.0 [95%CI, 611.4-864.6] ng • h/mL) and postpartum period (874.9 [95%CI, 408.2-1342.0] ng• h/mL). The rosuvastatin AUC0-last values did not differ between healthy nonpregnant women (13.8 [95%CI, 10.0-17.6] ng • h/mL) and women living with HIV in the postpartum period (13.3 [95%CI, 9.3-17.5] ng • h/mL), and the fexofenadine AUC0-last values did not differ between the 2 investigated groups (603.6 [95%CI, 467.5-739.7] ng • h/mL vs 874.9 [95%CI, 408.2-1342.0] ng • h/mL). It is suggested that gestation inhibits the hepatic OATP1B1/1B3 and/or BCRP activity but does not alter intestinal P-gp activity. The influence of HIV infection in conjunction with use of cART on OATP1B/BCRP and intestinal P-gp activity was not observed.
Keywords: cART; drug transporters; fexofenadine; pregnancy; rosuvastatin.
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