Tipiracil

Tipiracil Uses, Dosage, Side Effects, Food Interaction and all others data.

Tipiracil is a thymidine phosphorylase inhibitor. It is used in combination with trifluridine, in a ratio of 1:0.5, to form TAS-102. The main function of Tipiracil in TAS-102 is to increase trifluridine bioavailability by inhibiting its catabolism. TAS-102 is indicated for the treatment of metastatic colorectal cancer which has been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, or with an anti-VEGF or anti-EGFR therapy.

Tipiracil prevents trifluridine conversion into 5-trifluoromethyl-2,4(1H,3H)-pyrimidinedione, which is an inactive major metabolite, by inhibiting the enzyme thymidine phosphorylase. Thus, tipiracil is able to increase trifluridine bioavailability. On the other hand, thymidine phsophorylase is a known platelet-derived endothelial cell growth factor and its inhibition generates an indirect antiangiogenic benefit.

Tipiracil
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Tipiracil
Generic	Tipiracil
Tipiracil Other Names	Tipiracil, Tipiracilo
Type
Formula	C₉H₁₁ClN₄O₂
Weight	Average: 242.662 Monoisotopic: 242.057053323
Protein binding	Tipiracil does not bind highly to proteins and presents a plasma protein binding below 8%.
Groups	Approved, Investigational
Therapeutic Class
Manufacturer
Available Country
Last Updated:	September 19, 2023 at 7:00 am

Uses

Tipiracil is a thymidine phosphorylase inhibitor used as an adjunct treatment of adult patients with certain types of gastric or colorectal malignancies.

Tipiracil, in combination with trifluridine, is indicated for the treatment of refractory mestastatic colorectal cancer patients who keep progressing despite of treatment with standard chemotherapy and biologics.

Tipiracil is also used to associated treatment for these conditions: Metastatic Colorectal Cancer (MCRC)

How Tipiracil works

Tipiracil is a thymidine phosphorylase inhibitor. Its function prevents the breakdownof the active component of trifluridine, thus increasing the bioavailability of trifluridine and boosting its systemic presence. In addition, it is reported that thymidine phosphorylase is an angiogenic factor usually overexpressed in solid tumors. There is a direct association of thymidine phosphorylase with a poor prognosis; where the tumors with an elevated expression of this enzyme tend to present an increased angiogenesis and ergo, be more malignant. Therefore, it has been suggested that tipiracil presents an aditional function by downregulating tumoral angiogenesis.

Toxicity

TAS-102 is a cytotoxic drug, therefore this combination drug can cause myelosupression, including neutropenia, anemia, thrombocytopenia, and febrile neutropenia. According to pre-clinical studies, TAS-102 presents also embryo-fetal toxicity.

Food Interaction

Take with food.

Volume of Distribution

After a single TAS-102 dose if 35 mg/m2 in patients with advanced solid tumors, it was recorded a volume of distribution of tipiracil of 333 L.

Elimination Route

Absorption of tipiracil is suggested to be done by the gastrointestinal tract. Administration of a single 35 mg/m2 dose of TAS-102 containing tipiracil and trifluridine, generates the absoprtion rates of tipiracil of AUC 301 ng h/ml, maximum observed plasma concentration (Cmax) 69 ng/ml and time for maximum observed plasma concentration (Tmax) 3 h. The consumption of a high-fat and high-calorie meal can decrease Cmax and AUC by 40%.

Half Life

Tipiracil mean elmination half-life is 2.1 hours.

Clearance

A single 35mg/m2 of TAS-102 in patients with advanced solid tumors produces a clearance rate of tipiracil of 109 L/hr, with a recovery rate of 77% of the total dose.

Elimination Route

The main fraction of tipiracil is excreted unchanged in the mainly in the faeces (49.7%) followed by the urine (27%). From the urine excretion 79.1% is accounted by unchanged tipiracil while 14% is 6-HMU. On the other hand, the faeces elimination analysis was formed by 48.2% unchanged tipiracil and 34.4% 6-HMU.