Moreira Fernanda de Lima, Melli Patrícia Pereira Dos Santos, Marques Maria Paula, Rocha Adriana, Nardotto Glauco Henrique Balthazar, Duarte Geraldo, Lanchote Vera Lucia
Department of Clinical Analysis, Food Science and Toxicology, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Department of Drugs and Medicines, Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
J Clin Pharmacol. 2023 Feb;63(2):219-227. doi: 10.1002/jcph.2152. Epub 2022 Oct 4.
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 (AUC ) 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 AUC 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 AUC 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 AUC 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.
本研究评估妊娠、HIV感染联合使用雷特格韦、拉米夫定和替诺福韦酯富马酸盐（联合抗逆转录病毒疗法[cART]）对肠道P-糖蛋白（P-gp）、肝脏有机阴离子转运多肽（OATP）1B1/1B3和/或乳腺癌耐药蛋白（BCRP）药物转运活性的影响，采用瑞舒伐他汀（OATP1B/BCRP）和非索非那定（P-gp）探针。对妊娠晚期接受cART治疗的HIV感染女性（n = 15）和产后女性（n = 10）口服单剂量5 mg瑞舒伐他汀和60 mg非索非那定。还对12名健康未孕女性组成的对照组进行了研究。采用非房室方法估算药代动力学参数，并通过t检验进行评估（P < 0.05）。与产后（13.3 [95%CI，9.3 - 17.5] ng•h/mL）相比，妊娠晚期瑞舒伐他汀血浆浓度-时间曲线下从0至最后可定量浓度的面积（AUC）值更高（19.5 [95%CI，16.8 - 22.3] ng•h/mL），而非索非那定AUC值在妊娠晚期（738.0 [95%CI，611.4 - 864.6] ng•h/mL）和产后（874.9 [95%CI，408.2 - 1342.0] ng•h/mL）之间无差异。健康未孕女性（13.8 [95%CI，10.0 - 17.6] ng•h/mL）和产后HIV感染女性（13.3 [95%CI，9.3 - 17.5] ng•h/mL）的瑞舒伐他汀AUC值无差异，且两个研究组的非索非那定AUC值也无差异（603.6 [95%CI，467.5 - 739.7] ng•h/mL对874.9 [95%CI，408.2 - 1342.0] ng•h/mL）。提示妊娠会抑制肝脏OATP1B1/1B3和/或BCRP活性，但不会改变肠道P-gp活性。未观察到HIV感染联合使用cART对OATP1B/BCRP和肠道P-gp活性的影响。
