A single‐centre, open‐label, single‐arm, fixed‐sequence pharmacokinetic study of SHR3680 on repaglinide and bupropion in prostate cancer patients

To evaluate the pharmacokinetic effects of SHR3680 on repaglinide and bupropion and its metabolite hydroxybupropion. METHODS: A single‐centre, open‐label, single‐arm, fixed‐sequence clinical trial in 18 patients with prostate cancer. RESULTS: After a single oral dose of 0.5 mg repaglinide and SHR3680, geometric mean peak plasma concentration (C(max)) of plasma repaglinide was 14.240 and 5.887 ng/mL, geometric mean area under the concentration–time curve (AUC(0–t))was 20.577 and 7.320 h ng/mL, geometric mean AUC(0–∞) was 20.949 and 7.451 h ng/mL, mean half‐life (t(1/2)) was 1.629 and 1.195 hours, and geometric mean oral clearance (CL/F) was 23.867 and 67.107 L/h, respectively. After a single oral administration of 150 mg bupropion and SHR3680, geometric mean C(max) of plasma bupropion was 85.430 and 33.747 ng/mL, geometric mean AUC(0–t) was 1003.896 and 380.158 h ng/mL, geometric mean AUC(0–∞) was 1038.054 and 401.387 h ng/mL, mean t(1/2) was 22.533 and 17.733 hours, and geometric mean CL/F was 144.501 and 373.705 L/h, respectively. The plasma geometric mean C(max) of its main active metabolic hydroxybupropion was 268.113 and 177.318 ng/mL, geometric mean AUC(0–t) was 14 283.087 and 5420.219 h ng/mL, geometric mean AUC(0–∞) was 15 218.158 and 5364.625 h ng/mL, mean t(1/2) were 36.069 and 16.688 hours, and geometric mean CL/F was 8.623 L/h and 27.961 L/h, respectively. CONCLUSION: Coadministration of SHR3680 with repaglinide or bupropion significantly shortened the elimination half‐lives, significantly increased the apparent clearance rate, and significantly decreased the in vivo exposure of repaglinide, bupropion and hydroxybupropion compared with single administration of repaglinide or bupropion.