Relevance of pharmacogenetic aspects of mercaptopurine metabolism in the treatment of interstitial lung disease.
OBJECTIVE
Mercaptopurine therapy is increasingly important as immunosuppressive therapy in interstitial lung disease. We focus on human mercaptopurine metabolism and the defects in this metabolism causing adverse drug reactions.


RESULTS
Defects in mercaptopurine metabolizing enzymes like thiopurine methyltransferase and inosine triphosphate pyrophosphohydrolase lead to severe adverse drug reactions, sometimes with fatal outcome. Other enzymes, still not thoroughly investigated, can give rise to toxic effects or decreased efficacy in mercaptopurine therapy when the activity of these enzymes is altered.


CONCLUSIONS
Pharmacogenetic screening of potential patients for mercaptopurine therapy is important to avoid adverse drug reactions caused by inherited enzyme deficiencies in these metabolic pathways. Pretreatment screening for deficiencies of mercaptopurine metabolizing enzymes will significantly reduce the number of patients with an adverse drug reaction and concomitantly associated healthcare costs.
Bakker
Jaap A
JA
Department of Clinical Genetics, The Netherlands. jaap.bakker@gen.unimaas.nl
Drent
Marjolein
M
Bierau
Jörgen
J
D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D017563:Lung Diseases, Interstitial / Q000188:drug therapy*; D008403:Mass Screening; D015122:Mercaptopurine / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use*; D010597:Pharmacogenetics
D007166:Immunosuppressive Agents; D015122:Mercaptopurine