Axitinib, as a VEGFR tyrosine kinase inhibitor, mainly exerts its anti-tumor effect by inhibiting angiogenesis, while also paying attention to the risk of interaction with drugs related to the CYP metabolic system. The following will explain the mechanism of action, clinical efficacy, and drug interactions, with a focus on analyzing the factors affecting blood drug concentration and contraindications for combination therapy.

1. Pharmacological mechanism of action

(1) Angiogenesis inhibition

Selective inhibition of VEGFR-1/2/3 tyrosine kinase with an IC50 of 0.1-0.3 nM, blocking endothelial cell proliferation and migration, resulting in a 60% -80% decrease in tumor microvascular density.

(2) Signal pathway intervention

By inhibiting PDGFR - β and c-KIT secondary targets, interfering with tumor cell paracrine pathways, and enhancing anti vascular effects.

2. Clinical treatment effect

(1) Renal cell carcinoma

The median PFS of second-line treatment reached 6.7 months, with an objective response rate of 19.4%, significantly better than the sorafenib group (4.7 months).

(2) Dose-response relationship

At 5mgbid, the AUC0-24 was 150ng · h/mL, and the nonlinear pharmacokinetic characteristics were evident as the dose increased to 10mgbid.

3. Drug interactions

(1) CYP3A4 related

Strong inhibitors (such as ketoconazole) increase AUC by 2.1 times and require a 50% reduction; Inducing agents (such as rifampicin) reduce AUC by 71% and require an increase to 7mgbid.

(2) Transport protein influence

The combination with P-gp/BCRP substrates (such as digoxin) may increase the blood drug concentration of the latter, and adverse reactions need to be monitored.

(3) Gastric acid regulator

PPIs can reduce AUC by 21%, and it is recommended to use H2 receptor antagonists 10 hours before or 2 hours after administration.

(4) Special interactions

Avoiding the use of drugs that prolong the QT interval (such as clarithromycin) in combination may increase the risk of apical torsion ventricular tachycardia.