Capivasertib is a potent, selective inhibitor of all 3 Akt isoforms (Akt1/2/3), and it is currently being tested in Phase III trials for the treatment of prostate and breast cancer. To investigate the effect of a cytochrome P450 3A4 (CYP3A4) inhibitor on the pharmacokinetics of capivasertib, a Phase I drug–drug interaction study of capivasertib and itraconazole was conducted in 11 healthy volunteers (median age, 54 years). The 8-day study had 3 stages: Participants received a single dose of capivasertib 80 mg in Stage 1, 4 doses of itraconazole 200 mg over 3 days in Stage 2, and a final dose of capivasertib 80 mg coadministered with itraconazole 200 mg in Stage 3. Capivasertib pharmacokinetics were examined in Stages 1 and 3. Itraconazole coadministration increased the maximum plasma concentration of capivasertib and total capivasertib exposure (area under the concentration–time curve from time of administration to infinity) by 1.70-fold (90% confidence interval, 1.56–1.86) and 1.95-fold (90% confidence interval, 1.82–2.10), respectively.

中文翻译：

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在存在和不存在 CYP3A4 抑制剂伊曲康唑的情况下，对健康志愿者施用 Akt 丝氨酸/苏氨酸蛋白激酶抑制剂 Capivasertib 的药代动力学

Capivasertib 是所有 3 种 Akt 亚型 (Akt1/2/3) 的有效选择性抑制剂，目前正在用于治疗前列腺癌和乳腺癌的 III 期试验中进行测试。为了研究细胞色素 P450 3A4 (CYP3A4) 抑制剂对 capivasertib 药代动力学的影响，在 11 名健康志愿者（中位年龄 54 岁）中进行了 capivasertib 和伊曲康唑的 I 期药物相互作用研究。这项为期 8 天的研究分为 3 个阶段：第 1 阶段参与者接受单剂量 80 mg 的 capivasertib，第 2 阶段参与者在 3 天内接受 4 剂伊曲康唑 200 mg，第 2 阶段参与者接受最终剂量的 80 mg capivasertib 与 200 mg 伊曲康唑联合给药3. 在第 1 阶段和第 3 阶段检查 Capivasertib 药代动力学。伊曲康唑共同给药使 Capivasertib 的最大血浆浓度和总 Capivasertib 暴露量（从给药时间到无穷大的浓度-时间曲线下面积）增加 1.70 倍（90% 置信区间，分别为 1.56–1.86）和 1.95 倍（90% 置信区间，1.82–2.10）。