■SHR6390是口头的,有效和选择性的小分子CDK4/6抑制剂,用于治疗人类乳腺,卵巢癌和结肠癌。先前的研究表明,SHR6390与利福平联合使用,CYP3A4的有效诱导剂,显着降低暴露水平。因此,我们进一步研究了依非韦伦的作用,中等CYP3A4诱导剂,健康志愿者单次口服SHR6390。
■20名健康受试者参加了这个单中心,打开,单剂量,自控DDI研究。在第1天,受试者接受150mgSHR6390的单次口服剂量;在第8-26天,受试者在夜间口服600mg依非韦仑,在第22天单剂量150mgSHR6390。收集用于药代动力学分析的血液样品。
■联合治疗和SHR6390单药治疗(联合治疗/SHR6390单药治疗)之间的最大浓度(Cmax)和浓度曲线下面积(AUC0-inf)的几何平均比及其90%置信区间为0.562(0.482,0.654)和0.328(0.278,0.386),分别。这表明SHR6390的Cmax和AUC0inf下降了大约43.8%和67.2%,分别。在健康受试者中,单独或与依非韦仑一起口服150mgSHR6390是安全且可耐受的。
■建议在适度的CPY3A4诱导剂efavirenz的作用下,SHR6390的暴露AUC表现出中等水平的诱导。建议在用SHR6390治疗期间避免伴随施用CYP3A4的中度诱导剂。
■http://www.chinadrugtrials.org.cn/index。html,CTR20211571/https://classic.clinicaltrials.gov,NCT04973020。
UNASSIGNED: SHR6390 is an oral, potent and selective small-molecule CDK4/6 inhibitor for the treatment of human breast, ovarian and colon cancer. Previous studies have shown that SHR6390 in combination with rifampicin, a potent inducer of CYP3A4, significantly reduces exposure levels. Therefore, we further investigated the effect of efavirenz, a moderate CYP3A4 inducer, on a single oral dose of SHR6390 in healthy volunteers.
UNASSIGNED: Twenty healthy subjects were enrolled in this single-center, open, single-dose, self-controlled DDI study. On Day 1, subjects received a single oral dose of 150mg SHR6390; on Day 8-26, subjects received 600 mg efavirenz orally at night, with a single dose of 150 mg SHR6390 on Day 22. Blood samples for pharmacokinetic analyses were collected.
UNASSIGNED: The geometric mean ratios of the maximum concentration(Cmax) and the area under the concentration curve from zero to infinity (AUC0-inf) between combination therapy and SHR6390 monotherapy (combination therapy/SHR6390 monotherapy) and their 90% confidence intervals were 0.562 (0.482, 0.654) and 0.328 (0.278, 0.386), respectively. This indicates that the Cmax and AUC0 inf of SHR6390 decreased by approximately 43.8% and 67.2%, respectively. Oral administration of 150 mg SHR6390 alone or together with efavirenz was safe and tolerable in healthy subjects.
UNASSIGNED: It is suggested that under the action of the moderate CPY3A4 inducer efavirenz, the exposure AUC of SHR6390 exhibits a moderate level of induction. It is recommended to avoid concomitant administration of moderate inducers of CYP3A4 during treatment with SHR6390.
UNASSIGNED: http://www.chinadrugtrials.org.cn/index.html, CTR20211571/ https://classic.clinicaltrials.gov, NCT04973020.