Pharmacokinetics of gemcitabine in non-small-cell lung cancer patients: impact of the 79A > C cytidine deaminase polymorphism

Jan Gerard Maring; Floris M. Wachters; Monique Slijfer; Marina Maurer; H. Marike Boezen; Donald R. A. Uges; Elisabeth G. E. de Vries; Harry J. M. Groen

doi:10.1007/s00228-010-0799-0

Pharmacokinetics of gemcitabine in non-small-cell lung cancer patients: impact of the 79A > C cytidine deaminase polymorphism

Jan Gerard Maring^*, Floris M. Wachters, Monique Slijfer, Marina Maurer, H. Marike Boezen, Donald R. A. Uges, Elisabeth G. E. de Vries, Harry J. M. Groen

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

31 Citations (Scopus)

Abstract

To study the impact of the 79A > C polymorphism in the cytidine deaminase (CDA) gene on the pharmacokinetics of gemcitabine and its metabolite 2',2'-difluorodeoxyuridine (dFdU) in non-small-cell lung cancer (NSCLC) patients.

Patients (n = 20) received gemcitabine 1,125 mg/m(2) as a 30 min i.v. infusion as part of treatment for NSCLC. Plasma samples were collected during 0-6 h after gemcitabine administration. Gemcitabine and dFdU were quantified by high performance liquid chromatography with ultraviolet detection. The CDA 79A > C genotype was determined with PCR and DNA sequencing.

Gemcitabine was rapidly cleared from plasma and undetectable after 3 h. The allele frequency of the 79A > C polymorphism was 0.40. Diplotypes were distributed as A/A n = 8, A/C n = 8 ,and C/C n = 4. No significant differences were found between the different CDA genotypes and gemcitabine or dFdU AUC, clearance, or half-life.

The 79A > C polymorphism in the CDA gene does not have a major consistent and signficant impact on gemcitabine pharmacokinetics.

Original language	English
Pages (from-to)	611-617
Number of pages	7
Journal	European Journal of Clinical Pharmacology
Volume	66
Issue number	6
DOIs	https://doi.org/10.1007/s00228-010-0799-0
Publication status	Published - Jun-2010

Keywords

Gemcitabine
Cytidine deaminase
Pharmacogenetics
Pharmacokinetics
Genetic polymorphism
ADVANCED BREAST-CANCER
PHASE-III
EPIRUBICIN
2,2-DIFLUORODEOXYCYTIDINE
CISPLATIN
TOXICITY
PLASMA
TRIAL

Access to Document

10.1007/s00228-010-0799-0

Handle.net

Persistent link

Cite this

@article{3e612dfb65574e0a802f19593cfd9a82,

title = "Pharmacokinetics of gemcitabine in non-small-cell lung cancer patients: impact of the 79A > C cytidine deaminase polymorphism",

abstract = "To study the impact of the 79A > C polymorphism in the cytidine deaminase (CDA) gene on the pharmacokinetics of gemcitabine and its metabolite 2',2'-difluorodeoxyuridine (dFdU) in non-small-cell lung cancer (NSCLC) patients.Patients (n = 20) received gemcitabine 1,125 mg/m(2) as a 30 min i.v. infusion as part of treatment for NSCLC. Plasma samples were collected during 0-6 h after gemcitabine administration. Gemcitabine and dFdU were quantified by high performance liquid chromatography with ultraviolet detection. The CDA 79A > C genotype was determined with PCR and DNA sequencing.Gemcitabine was rapidly cleared from plasma and undetectable after 3 h. The allele frequency of the 79A > C polymorphism was 0.40. Diplotypes were distributed as A/A n = 8, A/C n = 8 ,and C/C n = 4. No significant differences were found between the different CDA genotypes and gemcitabine or dFdU AUC, clearance, or half-life.The 79A > C polymorphism in the CDA gene does not have a major consistent and signficant impact on gemcitabine pharmacokinetics.",

keywords = "Gemcitabine, Cytidine deaminase, Pharmacogenetics, Pharmacokinetics, Genetic polymorphism, ADVANCED BREAST-CANCER, PHASE-III, EPIRUBICIN, 2,2-DIFLUORODEOXYCYTIDINE, CISPLATIN, TOXICITY, PLASMA, TRIAL",

author = "Maring, {Jan Gerard} and Wachters, {Floris M.} and Monique Slijfer and Marina Maurer and Boezen, {H. Marike} and Uges, {Donald R. A.} and {de Vries}, {Elisabeth G. E.} and Groen, {Harry J. M.}",

year = "2010",

month = jun,

doi = "10.1007/s00228-010-0799-0",

language = "English",

volume = "66",

pages = "611--617",

journal = "European Journal of Clinical Pharmacology",

issn = "0031-6970",

publisher = "Springer Verlag",

number = "6",

}

TY - JOUR

T1 - Pharmacokinetics of gemcitabine in non-small-cell lung cancer patients

T2 - impact of the 79A > C cytidine deaminase polymorphism

AU - Maring, Jan Gerard

AU - Wachters, Floris M.

AU - Slijfer, Monique

AU - Maurer, Marina

AU - Boezen, H. Marike

AU - Uges, Donald R. A.

AU - de Vries, Elisabeth G. E.

AU - Groen, Harry J. M.

PY - 2010/6

Y1 - 2010/6

N2 - To study the impact of the 79A > C polymorphism in the cytidine deaminase (CDA) gene on the pharmacokinetics of gemcitabine and its metabolite 2',2'-difluorodeoxyuridine (dFdU) in non-small-cell lung cancer (NSCLC) patients.Patients (n = 20) received gemcitabine 1,125 mg/m(2) as a 30 min i.v. infusion as part of treatment for NSCLC. Plasma samples were collected during 0-6 h after gemcitabine administration. Gemcitabine and dFdU were quantified by high performance liquid chromatography with ultraviolet detection. The CDA 79A > C genotype was determined with PCR and DNA sequencing.Gemcitabine was rapidly cleared from plasma and undetectable after 3 h. The allele frequency of the 79A > C polymorphism was 0.40. Diplotypes were distributed as A/A n = 8, A/C n = 8 ,and C/C n = 4. No significant differences were found between the different CDA genotypes and gemcitabine or dFdU AUC, clearance, or half-life.The 79A > C polymorphism in the CDA gene does not have a major consistent and signficant impact on gemcitabine pharmacokinetics.

AB - To study the impact of the 79A > C polymorphism in the cytidine deaminase (CDA) gene on the pharmacokinetics of gemcitabine and its metabolite 2',2'-difluorodeoxyuridine (dFdU) in non-small-cell lung cancer (NSCLC) patients.Patients (n = 20) received gemcitabine 1,125 mg/m(2) as a 30 min i.v. infusion as part of treatment for NSCLC. Plasma samples were collected during 0-6 h after gemcitabine administration. Gemcitabine and dFdU were quantified by high performance liquid chromatography with ultraviolet detection. The CDA 79A > C genotype was determined with PCR and DNA sequencing.Gemcitabine was rapidly cleared from plasma and undetectable after 3 h. The allele frequency of the 79A > C polymorphism was 0.40. Diplotypes were distributed as A/A n = 8, A/C n = 8 ,and C/C n = 4. No significant differences were found between the different CDA genotypes and gemcitabine or dFdU AUC, clearance, or half-life.The 79A > C polymorphism in the CDA gene does not have a major consistent and signficant impact on gemcitabine pharmacokinetics.

KW - Gemcitabine

KW - Cytidine deaminase

KW - Pharmacogenetics

KW - Pharmacokinetics

KW - Genetic polymorphism

KW - ADVANCED BREAST-CANCER

KW - PHASE-III

KW - EPIRUBICIN

KW - 2,2-DIFLUORODEOXYCYTIDINE

KW - CISPLATIN

KW - TOXICITY

KW - PLASMA

KW - TRIAL

U2 - 10.1007/s00228-010-0799-0

DO - 10.1007/s00228-010-0799-0

M3 - Article

C2 - 20213492

SN - 0031-6970

VL - 66

SP - 611

EP - 617

JO - European Journal of Clinical Pharmacology

JF - European Journal of Clinical Pharmacology

IS - 6

ER -

Pharmacokinetics of gemcitabine in non-small-cell lung cancer patients: impact of the 79A > C cytidine deaminase polymorphism

Abstract

Keywords

Access to Document

Handle.net

Fingerprint

Cite this