Effects of Compound Kushen Injection on the Pharmacokinetics of Fluoxetine in Rats

ABSTRACT In clinical treatment, compound kushen injection (CKI) is often used in combination with fluoxetine (FLX) to enhance the therapeutic effect on tumor‐related depression in patients with tumors. To systematically investigate the pharmacokinetic interaction between CKI and FLX in plasma through UPLC–MS/MS analysis. Healthy male Sprague–Dawley rats were allocated to experimental or control groups; the experimental group received an injection of CKI (2 mg/kg) for 7 days, whereas the control group received an equivalent volume of saline. On Day 7, both groups received a single oral dose of FLX (10 mg/kg). Blood samples were subsequently collected from the tail vein at 15 time points over 72 h, after which the plasma concentrations of FLX were quantified using a validated UPLC–MS/MS method. The key pharmacokinetic parameters of FLX differed significantly ( p < 0.05 ) between the two groups. Compared with those in the control group, the AUC (0‐∞) , C max , and T 1/2z of FLX in the experimental group increased by 457.06%, 248.25%, and 90.62%, respectively, while CL/F, V z/ F, and T max decreased by 74.14%, 60.49%, and 41.11%, respectively. These findings demonstrate that CKI coadministration markedly alters FLX pharmacokinetics, potentially impacting treatment efficacy and safety.