Pyrimidine analogues

Pyrimidine analogues

Pyrimidine analogues are a diverse group of drugs that inhibitproduction of pyrimidine nucleotides necessary for DNA synthe-sis. They include:

·                 capecitabine

·                 cytarabine

·                 floxuridine

·                 fluorouracil

·                 gemcitabine.

Pharmacokinetics

Because pyrimidine analogues are poorly absorbed when they’re given orally, they’re usually administered by other routes.

Distribution, metabolism, and excretion

With the exception of cytarabine, pyrimidine analogues are well distributed throughout the body, including in cerebrospinal fluid (CSF). They’re metabolized extensively in the liver and are excret-ed in urine. Intrathecal cytarabine may be given with or without cranial radiation to treat CNS leukemia.

Pharmacodynamics

Pyrimidine analogues kill cancer cells by interfering with the nat-ural function ofpyrimidine nucleotides. (See How pyrimidineanalogues work.)

Pharmacotherapeutics

Pyrimidine analogues may be used to treat many tumors. Howev-er, they’re primarily indicated in the treatment of:

§    acute leukemias

§    GI tract adenocarcinomas, such as colorectal, pancreatic, esophageal, and stomach adenocarcinomas cancers of the breast and ovaries

§    malignant lymphomas.

Drug interactions

No significant drug interactions occur with most of the pyrimidine analogues; however, several drug interactions are possible with capecitabine.

·                 Antacids, when given with capecitabine, may increase absorption of capecitabine.

·                 Capecitabine can increase the pharmacodynamic effects of warfarin, thereby increasing the risk of bleeding.

·                 Capecitabine may increase serum phenytoin levels. (See Adverse reactions to pyrimidine analogues.)