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

Ivana Rizzuto, Essam Ghazaly, Godefridus J Peters

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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
JournalPharmacogenomics
Volume18
Issue number9
DOIs
Publication statusPublished - Jun 2017

Cite this

@article{e22288fa43a743ff95026cac5a4cf5df,
title = "Pharmacological factors affecting accumulation of gemcitabine's active metabolite, gemcitabine triphosphate",
abstract = "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.",
keywords = "Journal Article",
author = "Ivana Rizzuto and Essam Ghazaly and Peters, {Godefridus J}",
year = "2017",
month = "6",
doi = "10.2217/pgs-2017-0034",
language = "English",
volume = "18",
pages = "911--925",
journal = "Pharmacogenomics",
issn = "1462-2416",
publisher = "Future Medicine Ltd.",
number = "9",

}

Pharmacological factors affecting accumulation of gemcitabine's active metabolite, gemcitabine triphosphate. / Rizzuto, Ivana; Ghazaly, Essam; Peters, Godefridus J.

In: Pharmacogenomics, Vol. 18, No. 9, 06.2017, p. 911-925.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Pharmacological factors affecting accumulation of gemcitabine's active metabolite, gemcitabine triphosphate

AU - Rizzuto, Ivana

AU - Ghazaly, Essam

AU - Peters, Godefridus J

PY - 2017/6

Y1 - 2017/6

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.2217/pgs-2017-0034

DO - 10.2217/pgs-2017-0034

M3 - Article

VL - 18

SP - 911

EP - 925

JO - Pharmacogenomics

JF - Pharmacogenomics

SN - 1462-2416

IS - 9

ER -