Gemcitabine

Gemcitabine is a **synthetic pyrimidine nucleoside analog** used as an antineoplastic agent. - **Veterinary Use**: Currently considered investigational with limited clinical data. It shows potential as a **radiosensitizer** for non-resectable tumors or as part of combination chemotherapy protocols (e.g., with carboplatin). - **Human Use**: Efficacious in treating pancreatic, small-cell lung, bladder, and soft tissue carcinomas, as well as lymphoma. > **Clinical Pearl**: Due to its high cost and significant myelosuppressive potential, its use in veterinary medicine is typically reserved for specialized oncology practices.

กลไกการออกฤทธิ์: Gemcitabine is a **cell-cycle phase-specific** antimetabolite that acts primarily during the **S phase** (DNA synthesis) and blocks progression through the G1/S-phase boundary. - It is transported intracellularly and phosphorylated to **dFdCMP**, then to active diphosphate (**dFdCDP**) and triphosphate (**dFdCTP**) metabolites. - **dFdCDP** inhibits **ribonucleotide reductase**, depleting the cellular pool of deoxynucleotides required for DNA synthesis. - **dFdCTP** competes with endogenous deoxycytidine triphosphate (**dCTP**) for incorporation into the elongating DNA strand. Once incorporated, it causes **DNA chain termination** and subsequent apoptosis.

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