药物动力学和安全(S / GSK1349572,下一代HIV整合酶抑制剂,在健康的志愿者。

文章的细节

引用

复制到剪贴板

分钟年代,歌曲我,宝蓝J,陈年代,卢Y,藤原T, Piscitelli SC

药物动力学和安全(S / GSK1349572,下一代HIV整合酶抑制剂,在健康的志愿者。

Antimicrob代理Chemother。2010年1月,54 (1):254 - 8。doi: 10.1128 / AAC.00842-09。Epub 2009 11月2。

PubMed ID

19884365 (在PubMed

]

文摘

S / GSK1349572是一种新型的整合酶抑制剂与有效的体外抗艾滋病活性,体外抗概要文件不同于其他整合酶抑制剂,和良好的临床前安全性和药物动力学(PK)。随机、双盲、安慰剂对照单剂和multiple-dose剂量升级研究评估了PK,安全性和耐受性的S / GSK1349572健康受试者。在单剂的研究中,两个群10个科目(8活跃,2接受安慰剂)收到暂停剂量的2、5、10、25、50和100毫克的交替面板设计。multiple-dose研究中,三组10个科目每个(8活跃,2接受安慰剂)收到悬剂10日25日和50毫克每天一次10天。细胞色素P450 3 (CYP3A) substudy与咪达唑仑是25毫克剂量。实验室测试、生命体征、心电图(ecg)和定期采样进行PK。S / GSK1349572耐受性良好。大多数不良事件(AEs)是温和的,有一些温和的AEs报道。头痛是最常见的AE。没有明显临床实验室趋势或心电图变化。 PK was linear over the dosage range studied. The steady-state geometric mean area under the concentration-time curve over a dosing interval (AUC(0-tau)) and maximum concentration of the drug in plasma (C(max)) ranged from 16.7 microg.h/ml (coefficient of variation [CV], 15%) and 1.5 microg/ml (CV, 24%) at a 10-mg dose to 76.8 microg.h/ml (CV, 19%) and 6.2 microg/ml (CV, 15%) at a 50-mg dose, respectively. The geometric mean steady-state concentration at the end of the dosing interval (C(tau)) with a 50-mg dose was 1.6 microg/ml, approximately 25-fold higher than the protein-adjusted 90% inhibitory concentration (0.064 microg/ml). The half-life was approximately 15 h. S/GSK1349572 had no impact on midazolam exposure, indicating that it does not modulate CYP3A activity. The PK profile suggests that once-daily, low milligram doses will achieve therapeutic concentrations.

DrugBank数据引用了这篇文章

药物

Dolutegravir