Urinary Ratio of the Coproporphyrins Isomers I and III and Its Relationships With Methotrexate Elimination in Patients With a Lymphoid Malignancy
MTX is a substrate of MRP2, a renal tubular transporter encoded by the ABCC2 gene. It has
been shown that single nucleotide polymorphisms (SNPs) on the ABCC2 gene are associated with
impairment of MTX elimination. Mutations on the ABCC2 gene are also responsible for the
Dubin-Johnson syndrome, characterised by the absence of a functional MRP2 protein. Apart
from hyperbilirubinaemia, the main biological perturbation observed in this disease is a
typical increase of the urinary ratio of coproporphyrins I (I+ III) (UCP ratio). Our
hypothesis is that the UCP ratio could be used as a biomarker of MRP2's activity, thus
predicting MTX elimination. One hundred patients treated with high dose MTX will be
recruited in this prospective study. Their UCP ratio will be measured before and after MTX
administration and correlated with MTX clearance. A genetic analysis will be conducted to
study the five more frequents SNPs of ABCC2 in each patient.
Observational
Time Perspective: Cross-Sectional
MTX concentrations
at the end of MTX infusion and every 24-hours until concentrations reach 0,2µM.
Yes
Chantal Le Guellec, PharmD, PhD
Principal Investigator
CHRU of Tours
France: Ministry of Health
P061005
NCT00822432
October 2007
August 2011
Name | Location |
---|