Anticancer Drugs Oncology Pharmacology Physiotherapy Talazoparib

Talazoparib (Mechanism of Action)

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

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

Mechanism of Action

Talazoparib is an inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, including PARP1 and PARP2, which play a role in DNA repair. In vitro studies with cancer cell lines that harbored defects in DNA repair genes, including BRCA 1 and 2, have shown that talazoparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes resulting in DNA damage, decreased cell proliferation, and apoptosis. Talazoparib anti-tumor activity was observed in human patient-derived xenograft breast cancer tumor models that expressed mutated or wild-type BRCA 1 and 2.


Cardiac Electrophysiology

The effect of talazoparib on cardiac repolarization was evaluated in 37 patients with advanced solid tumors. Talazoparib had no large QTc prolongation (i.e., >20 ms) at the recommended dose.


After oral administration of 1 mg talazoparib once daily in patients, the recommended dose, the geometric mean [% coefficient of variation (CV%)] of AUC and maximum observed plasma concentration (Cmax) of talazoparib at steady-state was 208 (37%) and 16.4 (32%) ng/mL, respectively. The pharmacokinetics (PK) of talazoparib is linear from 0.025 mg to 2 mg (2 times the recommended dose). The median accumulation ratio of talazoparib following repeated oral administration of 1 mg once daily was in the range of 2.3 to 5.2. Talazoparib plasma concentrations reached steady-state within 2 to 3 weeks.


Following oral administration of talazoparib, the median time to Cmax (Tmax) was generally between 1 to 2 hours after dosing.

Food Effect

Following a single oral dose of 0.5 mg talazoparib with high-fat, high-calorie food (approximately 800 to 1000 calories with 150, 250, and 500 to 600 calories from protein, carbohydrate, and fat, respectively), the mean Cmax of talazoparib was decreased by 46%, the median Tmax was delayed from 1 to 4 hours, and AUCinf was not affected.


The mean apparent volume of distribution of talazoparib is 420 L. In vitro, protein binding of talazoparib is 74% and is independent of talazoparib concentration.


The mean terminal plasma half-life (┬▒standard deviation) of talazoparib is 90 (┬▒58) hours, and the mean apparent oral clearance (inter-subject variability) is 6.45 L/h (31.1%) in cancer patients.


Talazoparib undergoes minimal hepatic metabolism. The identified metabolic pathways of talazoparib in humans include mono-oxidation, dehydrogenation, cysteine conjugation of mono-desfluoro-talazoparib, and glucuronide conjugation.


Excretion of talazoparib in urine was the major route of elimination. Approximately 68.7% (54.6% unchanged) of the total administered radioactive dose [14C]talazoparib was recovered in urine, and 19.7% (13.6% unchanged) was recovered in feces.

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