Drug Groups

approved

Description

Gemcitabine is a nucleoside analog used as chemotherapy. It is marketed as Gemzar? by Eli Lilly and Company. As with fluorouracil and other analogues of pyrimidines, the drug replaces one of the building blocks of nucleic acids, in this case cytidine, during DNA replication. The process arrests tumor growth, as new nucleosides cannot be attached to the "faulty" nucleoside, resulting in apoptosis (cellular "suicide").
Gemcitabine is used in various carcinomas: non-small cell lung cancer, pancreatic cancer, bladder cancer and breast cancer. It is being investigated for use in oesophageal cancer, and is used experimentally in lymphomas and various other tumor types.

Indication

For the first-line treatment of patients with metastatic breast cancer, locally advanced (Stage IIIA or IIIB), or metastatic (Stage IV) non-small cell lung cancer and as first-line treatment for patients with adenocarcinoma of the pancreas.

Pharmacology

Gemcitabine is an antineoplastic anti-metabolite. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (or DNA synthesis phase of the cell cycle), stopping normal development and division. Gemcitabine blocks an enzyme which converts the cytosine nucleotide into the deoxy derivative. In addition, DNA synthesis is further inhibited because Gemcitabine blocks the incorporation of the thymidine nucleotide into the DNA strand.

Toxicity

Myelosuppression, paresthesias, and severe rash were the principal toxicities, LD₅₀=500 mg/kg (orally in mice and rats)

Affected Organisms

Biotransformation

Transformed via nucleoside kinases to two active metabolites, gemcitabine diphosphate and gemcitabine triphosphate. Can also undergo deamination via cytidine deaminase to an inactive uracil metabolite (dFdU).

Absorption

100%

Half Life

Short infusions ranged from 32 to 94 minutes, and the value for long infusions vary from 245 to 638 minutes, depending on age and gender.

Protein Binding

Plasma protein binding is negligible (<10%)

Distribution

* 50 L/m^2 [infusions lasting <70 minutes]
* 370 L/m^2 [long infusions]

Clearance

* 92.2 L/hr/m2 [Men 29 yrs]
* 75.7 L/hr/m2 [Men 45 yrs]
* 55.1 L/hr/m2 [Men 65 yrs]
* 40.7 L/hr/m2 [Men 79 yrs]
* 69.4 L/hr/m2 [Women 29 yrs]
* 57 L/hr/m2 [Women 45 yrs]
* 41.5 L/hr/m2 [Women 65 yrs]
* 30.7 L/hr/m2 [Women 79 yrs]

References

External Links