Pharmacological factors affecting accumulation of gemcitabine's active metabolite, gemcitabine triphosphate

Ivana Rizzuto, Essam Ghazaly, Godefridus J Peters

Research output: Contribution to journalArticleAcademicpeer-review


Gemcitabine is an anticancer agent acting against several solid tumors. It requires nucleoside transporters for cellular uptake and deoxycytidine kinase for activation into active gemcitabine-triphosphate, which is incorporated into the DNA and RNA. However, it can also be deaminated in the plasma. The intracellular level of gemcitabine-triphosphate is affected by scheduling or by combination with other chemotherapeutic regimens. Moreover, higher concentrations of gemcitabine-triphosphate may affect the toxicity, and possibly the clinical efficacy. As a consequence, different nucleoside analogs have been synthetized with the aim to increase the concentration of gemcitabine-triphosphate into cells. In this review, we summarize currently published evidence on pharmacological factors affecting the intracellular level of gemcitabine-triphosphate to guide future trials on the use of new nucleoside analogs.

Original languageEnglish
Pages (from-to)911-925
Number of pages15
Issue number9
Publication statusPublished - Jun 2017

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