Effects of ritonavir-boosted protease inhibitors on combined oral contraceptive pharmacokinetics and pharmacodynamics in HIV-positive women
Effects of ritonavir-boosted protease inhibitors on combined oral contraceptive pharmacokinetics and pharmacodynamics in HIV-positive women
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DOI：
10.1016/j.contraception.2019.06.002
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发表时间：
2019-10-01
期刊：
影响因子：
2.9
通讯作者：
Bender, Nicole M.
中科院分区：
文献类型：
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作者：
Barcellos, Teresa;Natavio, Melissa;Bender, Nicole M.
目的：评估联合口服避孕药（COC）成分的药代动力学和使用含利托那韦的抗逆转录病毒治疗方案的HIV阳性妇女的排卵率，并与使用先前发现与COC无相互作用的治疗方案或不使用任何抗逆转录病毒药物的妇女进行比较。我们进行了一项前瞻性队列药代动力学初步研究，比较了左炔诺孕酮（LNG）和炔雌醇（EE）在HIV感染者中的药代动力学。使用含利托那韦抗逆转录病毒治疗方案的阳性妇女与使用不含利托那韦治疗方案或不使用抗逆转录病毒治疗的妇女相比。受试者接受含LNG/EE 150/30 mcg的COC 21天。从第21天开始，我们在72小时内收集了一系列血液样本。主要结果是LNG的曲线下面积（AUC），次要结果包括其他LNG药代动力学指标，EE药代动力学和排卵测定的血清propherase.Results：LNG的药代动力学参数显示利托那韦的妇女暴露增加的趋势。与对照组（n=10）相比，服用利托那韦的女性的LNG AUC（last）增加了32.6%（312 +/- 60.9 vs. 243 +/- 82.6 ng/mL*h，p= 0.033，n=5）。利托那韦组的C-max（9.68 +/- 1.81 vs. 7.62 +/- 2.29 ng/mL）和C-min（4.97 +/- 1.15 vs. 3.70 +/- 1.29 ng/mL）也较高。排除不一致使用者（n=2）后，利托那韦组的LNG CL降低（p= 0.032）。EE药代动力学特征在组间无差异。两组妇女的孕酮浓度相似，没有一致的治疗cycle.Conclusion：利托那韦妇女显示约30%的LNG暴露量增加，但EE暴露量没有差异。(C)2019爱思唯尔公司All rights reserved.
Objective: To assess the pharmacokinetics of combined oral contraceptive (COC) components and prevalence of ovulation in HIV-positive women using ritonavir-containing antiretroviral regimens compared to those using regimens previously found not to interact with COCs or not using any antiretrovirals.Study design: We conducted a prospective cohort pharmacokinetic pilot study comparing the pharmacokinetics of levonorgestrel (LNG) and ethinyl estradiol (EE) in HIV-positive women taking ritonavir-containing antiretroviral regimens to those in women using non-ritonavir-containing regimens or no antiretrovirals. Participants received COCs containing LNG/EE 150/30 mcg for 21 days. Beginning day 21, we collected serial blood samples over 72 h. The primary outcome was area under the curve (AUC) of LNG, with secondary outcomes including other LNG pharmacokinetic measures, EE pharmacokinetics and ovulation as measured by serum progesterone.Results: Pharmacokinetic parameters of LNG showed a trend toward increased exposure in women on ritonavir. LNG AUC(last) increased by 32.6% (312 +/- 60.9 vs. 243 +/- 82.6 ng/mL*h, p=.033, n=5) in women taking ritonavir compared to the control group (n=10). The C-max (9.68 +/- 1.81 vs. 7.62 +/- 2.29 ng/mL) and C-min (4.97 +/- 1.15 vs. 3.70 +/- 1.29 ng/mL) were also higher in the ritonavir arm. After excluding the inconsistent users (n=2), CL of LNG was reduced in the ritonavir arm (p=.032). EE pharmacokinetic profiles were not different between groups. The progesterone concentrations were similar in women of both groups, and none were consistent with ovulation during the treatment cycle.Conclusion: Women on ritonavir showed an approximately 30% increase in LNG exposure but no difference in EE exposure. (C) 2019 Elsevier Inc. All rights reserved.