6-mercaptopurine therapy

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

6-Mercaptopurine (6-MP) and its pro-drug azathioprine have proven efficacy in the maintenance of disease remission in children with steroid-dependent Crohn's disease. However, not all patients respond effectively to therapy, while others are predisposed to drug-induced toxicity; thereby, suggesting that inherent differences in anti-metabolite metabolism may influence clinical responsiveness to therapy. Although genomic (TPMT) and drug metabolite monitoring have been available for greater than a decade, there is more debate than consensus on their application in clinical practice, primarily due to the lack of controlled clinical trials.Nevertheless, patients with a homozygous recessive TPMT genotype should not be considered candidates for anti-metabolite therapy. Physicians treating patients with a heterozygote genotype should consider a more moderate dosing strategy, while carefully monitoring for potential antimetabolite-induced cytotoxicity. In these patients, 6-MP-metabolite testing may help clinicians monitor immunosuppression and decrease the risk of toxicity. Future prospective clinical trials are necessary in order to develop a therapeutic window of clinical efficacy and toxicity based on the measurement of these drug metabolites.

Original languageEnglish (US)
Title of host publicationPediatric Inflammatory Bowel Disease, Second Edition
PublisherSpringer New York
Pages331-337
Number of pages7
ISBN (Electronic)9781461450610
ISBN (Print)9781461450603
DOIs
StatePublished - Jan 1 2013

Fingerprint

6-Mercaptopurine
Genotype
Antimetabolites
Drug Monitoring
Controlled Clinical Trials
Azathioprine
Prodrugs
Therapeutics
Heterozygote
Drug-Related Side Effects and Adverse Reactions
Crohn Disease
Immunosuppression
Steroids
Maintenance
Clinical Trials
Physicians
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Cuffari, C. (2013). 6-mercaptopurine therapy. In Pediatric Inflammatory Bowel Disease, Second Edition (pp. 331-337). Springer New York. https://doi.org/10.1007/978-1-4614-5061-0_31

6-mercaptopurine therapy. / Cuffari, Carmelo.

Pediatric Inflammatory Bowel Disease, Second Edition. Springer New York, 2013. p. 331-337.

Research output: Chapter in Book/Report/Conference proceedingChapter

Cuffari, C 2013, 6-mercaptopurine therapy. in Pediatric Inflammatory Bowel Disease, Second Edition. Springer New York, pp. 331-337. https://doi.org/10.1007/978-1-4614-5061-0_31
Cuffari C. 6-mercaptopurine therapy. In Pediatric Inflammatory Bowel Disease, Second Edition. Springer New York. 2013. p. 331-337 https://doi.org/10.1007/978-1-4614-5061-0_31
Cuffari, Carmelo. / 6-mercaptopurine therapy. Pediatric Inflammatory Bowel Disease, Second Edition. Springer New York, 2013. pp. 331-337
@inbook{8ef5a205f3eb4943a6a525897868db15,
title = "6-mercaptopurine therapy",
abstract = "6-Mercaptopurine (6-MP) and its pro-drug azathioprine have proven efficacy in the maintenance of disease remission in children with steroid-dependent Crohn's disease. However, not all patients respond effectively to therapy, while others are predisposed to drug-induced toxicity; thereby, suggesting that inherent differences in anti-metabolite metabolism may influence clinical responsiveness to therapy. Although genomic (TPMT) and drug metabolite monitoring have been available for greater than a decade, there is more debate than consensus on their application in clinical practice, primarily due to the lack of controlled clinical trials.Nevertheless, patients with a homozygous recessive TPMT genotype should not be considered candidates for anti-metabolite therapy. Physicians treating patients with a heterozygote genotype should consider a more moderate dosing strategy, while carefully monitoring for potential antimetabolite-induced cytotoxicity. In these patients, 6-MP-metabolite testing may help clinicians monitor immunosuppression and decrease the risk of toxicity. Future prospective clinical trials are necessary in order to develop a therapeutic window of clinical efficacy and toxicity based on the measurement of these drug metabolites.",
author = "Carmelo Cuffari",
year = "2013",
month = "1",
day = "1",
doi = "10.1007/978-1-4614-5061-0_31",
language = "English (US)",
isbn = "9781461450603",
pages = "331--337",
booktitle = "Pediatric Inflammatory Bowel Disease, Second Edition",
publisher = "Springer New York",

}

TY - CHAP

T1 - 6-mercaptopurine therapy

AU - Cuffari, Carmelo

PY - 2013/1/1

Y1 - 2013/1/1

N2 - 6-Mercaptopurine (6-MP) and its pro-drug azathioprine have proven efficacy in the maintenance of disease remission in children with steroid-dependent Crohn's disease. However, not all patients respond effectively to therapy, while others are predisposed to drug-induced toxicity; thereby, suggesting that inherent differences in anti-metabolite metabolism may influence clinical responsiveness to therapy. Although genomic (TPMT) and drug metabolite monitoring have been available for greater than a decade, there is more debate than consensus on their application in clinical practice, primarily due to the lack of controlled clinical trials.Nevertheless, patients with a homozygous recessive TPMT genotype should not be considered candidates for anti-metabolite therapy. Physicians treating patients with a heterozygote genotype should consider a more moderate dosing strategy, while carefully monitoring for potential antimetabolite-induced cytotoxicity. In these patients, 6-MP-metabolite testing may help clinicians monitor immunosuppression and decrease the risk of toxicity. Future prospective clinical trials are necessary in order to develop a therapeutic window of clinical efficacy and toxicity based on the measurement of these drug metabolites.

AB - 6-Mercaptopurine (6-MP) and its pro-drug azathioprine have proven efficacy in the maintenance of disease remission in children with steroid-dependent Crohn's disease. However, not all patients respond effectively to therapy, while others are predisposed to drug-induced toxicity; thereby, suggesting that inherent differences in anti-metabolite metabolism may influence clinical responsiveness to therapy. Although genomic (TPMT) and drug metabolite monitoring have been available for greater than a decade, there is more debate than consensus on their application in clinical practice, primarily due to the lack of controlled clinical trials.Nevertheless, patients with a homozygous recessive TPMT genotype should not be considered candidates for anti-metabolite therapy. Physicians treating patients with a heterozygote genotype should consider a more moderate dosing strategy, while carefully monitoring for potential antimetabolite-induced cytotoxicity. In these patients, 6-MP-metabolite testing may help clinicians monitor immunosuppression and decrease the risk of toxicity. Future prospective clinical trials are necessary in order to develop a therapeutic window of clinical efficacy and toxicity based on the measurement of these drug metabolites.

UR - http://www.scopus.com/inward/record.url?scp=84956620875&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84956620875&partnerID=8YFLogxK

U2 - 10.1007/978-1-4614-5061-0_31

DO - 10.1007/978-1-4614-5061-0_31

M3 - Chapter

AN - SCOPUS:84956620875

SN - 9781461450603

SP - 331

EP - 337

BT - Pediatric Inflammatory Bowel Disease, Second Edition

PB - Springer New York

ER -