Impact of steady state Cobicistat and Darunavir/Cobicistat And on the Pharmacokinetics And Pharmacodynamics of Oral Anticoagulants (Rivaroxaban, Apixaban) In Healthy Volunteers (CLOTRX)
稳态考比司他和达芦那韦/考比司他对健康志愿者中口服抗凝剂(利伐沙班、阿哌沙班)药代动力学和药效学的影响 (CLOTRX)
基本信息
- 批准号:10928540
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至
- 项目状态:未结题
- 来源:
- 关键词:Activated Partial Thromboplastin Time measurementAnti-Retroviral AgentsAnticoagulantsAnticoagulationAreaArea Under CurveCYP3A4 geneClinicalCoagulation ProcessCoupledCytochrome P450DataDiseaseDoseDrug InteractionsDrug KineticsEnzymesEventFactor XaFood-Drug InteractionsGenesGenetic PolymorphismGlycoproteinsHIVHIV SeronegativityHalf-LifeHemorrhageHourIsoenzymesLaboratoriesMonitorOralPatientsPermeabilityPersonsPharmaceutical PreparationsPharmacodynamicsPlasmaPopulationPreventionPropertyRegimenRoleSafetySecurityTimeTransportationWarfarinabsorptionantiretroviral therapyhealthy volunteerhigh riskinhibitorliver metabolismmedication safetymetabolic abnormality assessmentpharmacokinetics and pharmacodynamicsprimary endpointsecondary endpoint
项目摘要
Rivaroxaban is a direct oral anticoagulant (DOAC) used for the prevention and treatment of various thromboembolic disorders. Predictable pharmacokinetic (PK) and pharmacodynamic (PD) properties, coupled with a few drug-drug and food-drug interactions, distinguishes DOACs from traditionally used anticoagulant - warfarin, allowing fixed dosing without routine coagulation monitoring. Patients with human immunodeficiency virus (HIV) are living as long as their HIV negative counterparts due to safe and efficacious antiretroviral therapy (ART). Persons with HIV are at higher risk for thromboembolic events and DOACs are a feasible option for anticoagulation in this population. However, there is a lack of drug interaction and safety data currently on the co-administration cobicistat (COBI)-boosted antiretroviral (ARV) regimens with rivaroxaban. Rivaroxaban is metabolized by cytochrome P450 isozyme (CYP) 3A4 and its absorption is modulated by permeability-glycoprotein (P-gp), both of which are inhibited by the PK booster COBI. It is therefore possible that plasma concentrations of rivaroxaban may be significantly increased when co-administered together with COBI. This is of clinical concern as increased anticoagulant exposure may result in bleeding without the security of routine clinical monitoring. The purpose of this study is to determine the effects of steady state concentrations of COBI and DRV/COBI on the PK and PD of single oral doses of rivaroxaban.
利伐沙班是一种直接口服抗凝剂(DOAC),用于预防和治疗各种血栓栓塞性疾病。可预测的药代动力学(PK)和药效学(PD)特性,加上一些药物-药物和食物-药物相互作用,将DOAC与传统使用的抗凝剂-华法林区分开来,允许固定剂量而无需常规凝血监测。由于安全有效的抗逆转录病毒治疗(ART),人类免疫缺陷病毒(HIV)患者的寿命与HIV阴性患者一样长。HIV感染者发生血栓栓塞事件的风险较高,DOAC是该人群抗凝治疗的可行选择。 然而,目前缺乏关于cobicistat(COBI)加强抗逆转录病毒(ARV)方案与利伐沙班联合给药的药物相互作用和安全性数据。 利伐沙班通过细胞色素P450同工酶(CYP)3A 4代谢,其吸收通过渗透性糖蛋白(P-gp)调节,这两种代谢途径均受到PK加强剂COBI的抑制。因此,当与COBI共同给药时,利伐沙班的血浆浓度可能显著增加。这是一个临床问题,因为抗凝剂暴露增加可能导致出血,而常规临床监测不安全。本研究的目的是确定COBI和DRV/COBI的稳态浓度对利伐沙班单次口服给药的PK和PD的影响。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
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Jomy George其他文献
Jomy George的其他文献
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{{ truncateString('Jomy George', 18)}}的其他基金
Impact of Once-Weekly Rifapentine and Isoniazid on the Steady State Pharmacokinetics of Dolutegravir and Darunavir Boosted with Cobicistat in Healthy Volunteers (R2D2)
每周一次利福喷丁和异烟肼对健康志愿者中用考比司他增强的多替拉韦和达芦那韦稳态药代动力学的影响 (R2D2)
- 批准号:
10253690 - 财政年份:
- 资助金额:
-- - 项目类别:
Impact of Once-Weekly Rifapentine and Isoniazid on the Steady State Pharmacokinetics of Dolutegravir and Darunavir Boosted with Cobicistat in Healthy Volunteers (R2D2)
每周一次利福喷丁和异烟肼对健康志愿者中用考比司他增强的多替拉韦和达芦那韦稳态药代动力学的影响 (R2D2)
- 批准号:
10471698 - 财政年份:
- 资助金额:
-- - 项目类别:
Impact of steady state Cobicistat and Darunavir/Cobicistat And on the Pharmacokinetics And Pharmacodynamics of Oral Anticoagulants (Rivaroxaban, Apixaban) In Healthy Volunteers (CLOTRX)
稳态考比司他和达芦那韦/考比司他对健康志愿者中口服抗凝剂(利伐沙班、阿哌沙班)药代动力学和药效学的影响 (CLOTRX)
- 批准号:
10471699 - 财政年份:
- 资助金额:
-- - 项目类别:
Impact of Once-Weekly Rifapentine and Isoniazid on the Steady State Pharmacokinetics of Dolutegravir and Darunavir Boosted with Cobicistat in Healthy Volunteers (R2D2)
每周一次利福喷丁和异烟肼对健康志愿者中用考比司他增强的多替拉韦和达芦那韦稳态药代动力学的影响 (R2D2)
- 批准号:
9792180 - 财政年份:
- 资助金额:
-- - 项目类别:
The Influence of Cobicistat or Ritonavir on Dabigatran Pharmacokinetics and Phar
考比司他或利托那韦对达比加群药代动力学和药物的影响
- 批准号:
10019267 - 财政年份:
- 资助金额:
-- - 项目类别:
Impact of steady state Cobicistat and Darunavir/Cobicistat And on the Pharmacokinetics And Pharmacodynamics of Oral Anticoagulants (Rivaroxaban, Apixaban) In Healthy Volunteers (CLOTRX)
稳态考比司他和达芦那韦/考比司他对健康志愿者中口服抗凝剂(利伐沙班、阿哌沙班)药代动力学和药效学的影响 (CLOTRX)
- 批准号:
10019270 - 财政年份:
- 资助金额:
-- - 项目类别:
The Influence of Cobicistat or Ritonavir on Dabigatran Pharmacokinetics and Phar
考比司他或利托那韦对达比加群药代动力学和药物的影响
- 批准号:
10253688 - 财政年份:
- 资助金额:
-- - 项目类别:
Impact of steady state Cobicistat and Darunavir/Cobicistat And on the Pharmacokinetics And Pharmacodynamics of Oral Anticoagulants (Rivaroxaban, Apixaban) In Healthy Volunteers (CLOTRX)
稳态考比司他和达芦那韦/考比司他对健康志愿者中口服抗凝剂(利伐沙班、阿哌沙班)药代动力学和药效学的影响 (CLOTRX)
- 批准号:
10253691 - 财政年份:
- 资助金额:
-- - 项目类别:
Impact of Weekly Administration of RPT and INH on TAF Pharmacokinetics in Healthy Volunteers
每周服用 RPT 和 INH 对健康志愿者中 TAF 药代动力学的影响
- 批准号:
10019268 - 财政年份:
- 资助金额:
-- - 项目类别:
The Influence of Cobicistat or Ritonavir on Dabigatran Pharmacokinetics and Phar
考比司他或利托那韦对达比加群药代动力学和药物的影响
- 批准号:
10471696 - 财政年份:
- 资助金额:
-- - 项目类别:
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