ABCMdb

PMID: 19433977

Prandota J
Advances of molecular clinical pharmacology in gastroenterology and hepatology.
Am J Ther. 2010 Sep-Oct;17(5):e137-62., [PubMed]

Sentences

No. Mutations Sentence Comment

79 ABCC2 p.Gly460Ala ABCC2 p.Gly460Ala The patient`s age and renal function status may elicit changes in erythrocyte TPMT activity, and blood transfusion performed during the 2 months preceding treatment may lead to false results.8 In addition, drug interactions may also exert deleterious effects, for example, concomitant administration of AZA and mesalamine (often used in ulcerative colitis) leads to an increase in 6-TGN blood levels and enhances risk of myelotoxicity, which can be explained by reversible inhibition of mesalamine metabolism by TPMT.65,78 In the patients receiving both thiopurines and mesalamine, adverse effects were observed more frequently.78,79 TPMT activity may be inhibited also by therapeutic plasma levels of furosemide, thiazide diuretics, sulfasalazine, 5-acetylsalicylic acid, and nonsteroid antiinflammatory Table 7. Characteristics of thiopurine S-methyltransferase main alleles. Allele Functional nucleotide change Amino acid change Enzyme activity Associated phenotype Allele prevalence (%) TPMT*1 None None Normal EM 96.1 TPMT*2 G238C Ala80Pro Decreased PM 2-5 TPMT*3A G460A A719G Ala154Thr Tyr240Cys None PM 3.5-6.5 TMPT*3B G460A Ala154Thr None PM 0.35 TPMT*3C A719G Tyr240Cys None PM 0.7 PM, poor metabolizer; EM, efficient metabolizer drugs.67,80 Conversely, thiopurine therapy alone may increase activity of TPMT.8,65,73 In some cases, monitoring of therapeutic 6-TGN blood concentrations may be as important as TPMT genotyping or phenotyping. Login to comment