Anticancer Drugs Oncology Pharmacology Physiotherapy Tucatinib

Tucatinib (Mechanism of Action)

In this article we will discuss Tucatinib (Mechanism of Action)

In this article, we will discuss Tucatinib (Mechanism of Action). So, let’s get started.

Mechanism of Action

Tucatinib is a tyrosine kinase inhibitor of HER2. In vitro, tucatinib inhibits phosphorylation of HER2 and HER3, resulting in inhibition of downstream MAPK and AKT signaling and cell proliferation, and showed anti-tumor activity in HER2 expressing tumor cells. In vivo, tucatinib inhibited the growth of HER2 expressing tumors. The combination of tucatinib and trastuzumab showed increased anti-tumor activity in vitro and in vivo compared to either drug alone.


Exposure Response Relationship

Tucatinib exposure-response relationships and the time course of pharmacodynamics response have not been fully characterized.

Cardiac Electrophysiology

No large mean increase in QTc (i.e., > 20 ms) was detected following treatment with Tucatinib at the recommended dose of 300 mg taken orally twice daily.


Tucatinib AUC0-INF and Cmax increases proportionally over a dosage range from 50 mg to 300 mg (0.17 to 1 times the approved recommended dosage). Tucatinib exhibited 1.7-fold accumulation for AUC and 1.5-fold accumulation for Cmax following administration of Tucatinib 300 mg twice daily for 14 days. Time to steady state was approximately 4 days.


The median time to peak plasma concentration of tucatinib was approximately 2 hours (range 1 to 4 hours).

Effects of Food

Following administration of a single oral dose of Tucatinib in 11 subjects after a high-fat meal (approximately 58% fat, 26% carbohydrate, and 16% protein), the mean AUC0-INF increased by 1.5-fold, the Tmax shifted from 1.5 hours to 4 hours, and Cmax was unaltered. The effect of food on the pharmacokinetics of tucatinib was not
clinically meaningful.


The geometric mean (CV%) apparent volume of distribution of tucatinib was approximately 1670 L (66%). The
plasma protein binding was 97.1% at clinically relevant concentrations.


The geometric mean (CV%) half-life of tucatinib was approximately 8.5 (21%) hours and apparent clearance was 148 L/h (55%).


Tucatinib is metabolized primarily by CYP2C8 and to a lesser extent via CYP3A.


Following a single oral dose of 300 mg radiolabeled tucatinib, approximately 86% of the total radiolabeled dose was recovered in feces (16% of the administered dose as unchanged tucatinib) and 4.1% in urine with an overall total recovery of 90% within 13 days post-dose. In plasma, approximately 76% of the plasma radioactivity was unchanged, 19% was attributed to identified metabolites, and approximately 5% was unassigned.

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