Hepatocellular carcinoma (HCC) is a malignancy of liver cells. Recent studies have shown that HCC patients often have changes in the activities of transporters and metabolic enzymes, which can considerably affect drug pharmacokinetics and lead to drug toxicity. Doxorubicin (DOX) has been frequently administered in chemotherapy for HCC, but to our knowledge, the effects of HCC on the pharmacokinetics of DOX are unknown.

In the present study, following intravenous administration of DOX in diethylnitrosamine-induced HCC rats, the plasma concentration was determined by a UPLC/MS/MS method. The expression of metabolic enzyme and transporters (p-gp, cbr1 and slc22a16) was analyzed by qRT-PCR and western blot.

The results showed that the pharmacokinetic parameters AUC, T_1/2, K₁₂ and K₂₁ of DOX were markedly increased, the K₁₀ and CL were significantly decreased in HCC rats. The expression of cbr1 and slc22a16 was markedly decreased, while p-gp was significantly upregulated in HCC rats.

These findings suggest that HCC could significantly alter the pharmacokinetic profile of DOX, which may be associated with the decreased expression of cbr1 and slc22a16 rather than the upregulation of p-gp expression.

肝细胞癌（HCC）是肝细胞的恶性肿瘤。最近的研究表明，肝癌患者的转运蛋白和代谢酶活性经常发生变化，这可能会大大影响药物的药代动力学并导致药物毒性。阿霉素（DOX）在HCC的化疗中经常使用，但是据我们所知，HCC对DOX药代动力学的影响尚不清楚。

在本研究中，在二乙基亚硝胺诱导的HCC大鼠中静脉内施用DOX之后，通过UPLC / MS / MS方法测定血浆浓度。通过qRT-PCR和蛋白质印迹分析代谢酶和转运蛋白（p-gp，cbr1和slc22a16）的表达。

结果表明，HCC大鼠DOX的药代动力学参数AUC，T _1/2，K ₁₂和K ₂₁明显升高，K ₁₀和CL明显降低。在肝癌大鼠中，cbr1和slc22a16的表达明显降低，而p-gp则明显上调。

这些发现表明，HCC可以显着改变DOX的药代动力学特征，这可能与cbr1和slc22a16的表达降低有关，而不是与p-gp表达的上调有关。