Dolutegravir pharmacokinetics during co-administration with either artemether/lumefantrine or artesunate/amodiaquine.
Dolutegravir pharmacokinetics during co-administration with either artemether/lumefantrine or artesunate/amodiaquine.
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多替拉韦与蒿甲醚/本芴醇或青蒿琥酯/阿莫地喹联合给药期间的药代动力学。
DOI：
10.1093/jac/dkab022
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Kawuma AN
中科院分区：
文献类型：
--
作者：
Kawuma AN
背景在撒哈拉以南非洲，含有青蒿素的疟疾治疗方法定期与抗逆转录病毒治疗联合实施。目前，基于多洛替格雷的方案被推荐为大多数非洲地区HIV的一线治疗方案。目的研究多洛替格雷与蒿甲醚/鲁米芬或青蒿琥酯/阿莫地喹两种常用抗疟药合用时的群体药代动力学。方法我们利用26名健康志愿者的数据建立了多洛替格雷的群体药代动力学模型，共403人稳态血药浓度。受试者单用或与标准剂量的蒿甲醚/鲁米芬(80/480 mg)或青蒿琥酯/阿莫地喹(200/540 mg)合用，每日1次口服50 mg多洛替格雷。典型人群估计的清除率、吸收速率常数、中心体积、外周体积和平均吸收通过时间分别为0.713 L/h、1.68 h−1、13.2 L、5.73 L和1.18 h。联合应用蒿甲醚/鲁米芬或青蒿琥酯/阿莫地喹可使多洛替格韦清除率分别增加10.6%(95%CI 4.09%~34.5%)和26.4%(95%CI 14.3%~51.4%)。模拟结果显示，99%以上的患者单用或与蒿甲醚/卢米芬或青蒿琥酯/阿莫地喹联用的模拟低谷血药浓度维持在0.064 mg/L的多洛替格韦蛋白调整IC90以上。结论服用标准3 剂量蒿甲醚/卢米芬或青蒿琥酯/阿莫地喹的患者无需调整剂量。
BackgroundIn sub-Saharan Africa, artemisinin-containing therapies for malaria treatment are regularly co-administered with ART. Currently, dolutegravir-based regimens are recommended as first-line therapy for HIV across most of Africa.ObjectivesTo investigate the population pharmacokinetics of dolutegravir during co-administration with artemether/lumefantrine or artesunate/amodiaquine, two commonly used antimalarial therapies.MethodsWe developed a population pharmacokinetic model of dolutegravir with data from 26 healthy volunteers in two Phase 2 studies with a total of 403 dolutegravir plasma concentrations at steady state. Volunteers received 50 mg of dolutegravir once daily alone or in combination with standard treatment doses of artemether/lumefantrine (80/480 mg) or artesunate/amodiaquine (200/540 mg).ResultsA two-compartment model with first-order elimination and transit compartment absorption best described the concentration–time data of dolutegravir. Typical population estimates for clearance, absorption rate constant, central volume, peripheral volume and mean absorption transit time were 0.713 L/h, 1.68 h−1, 13.2 L, 5.73 L and 1.18 h, respectively. Co-administration of artemether/lumefantrine or artesunate/amodiaquine increased dolutegravir clearance by 10.6% (95% CI 4.09%–34.5%) and 26.4% (95% CI 14.3%–51.4%), respectively. Simulations showed that simulated trough concentrations of dolutegravir alone or in combination with artemether/lumefantrine or artesunate/amodiaquine are maintained above the dolutegravir protein-adjusted IC90of 0.064 mg/L for more than 99% of the individuals.ConclusionsDolutegravir dose adjustments are not necessary for patients who are taking standard 3 day treatment doses of artemether/lumefantrine or artesunate/amodiaquine.
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蒿甲醚和苯芴醇 (Riamet®) 的临床药代动力学
DOI：
--
发表时间：
1999
期刊：
影响因子：
--
作者：
G. Lefèvre;M. Thomsen
通讯作者：
M. Thomsen
多替拉韦
影响因子：
1
作者：
Candice J. Mercadel;Jessica W. Skelley;J. A. Kyle;L. Elmore
通讯作者：
L. Elmore
影响因子：
3.7
作者：
Guttman, Yelena;Nudel, Adi;Kerem, Zohar
通讯作者：
Kerem, Zohar
影响因子：
3.9
作者：
Reese, Melinda J.;Savina, Paul M.;Polli, Joseph W.
通讯作者：
Polli, Joseph W.
多替拉韦与蒿甲醚-卢美芴或青蒿琥酯-阿莫地喹之间药物相互作用的解释
影响因子：
4.9
作者：
C. G. Banda;K. Barnes;G. Maartens
通讯作者：
G. Maartens