A single-centre, open-label, single-arm, fixed-sequence pharmacokinetic study of SHR3680 on repaglinide and bupropion...

To evaluate the pharmacokinetic effects of SHR3680 on repaglinide and bupropion and its metabolite hydroxybupropion.

A single-centre, open-label, single-arm, fixed-sequence clinical trial in 18 patients with prostate cancer.

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.

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.