当前位置： SCI文献检索 > GUT期刊下所有文献 > Pharmacogenetics during standardised initiation of thiopurine treatment in inflammatory bowel disease.

Pharmacogenetics during standardised initiation of thiopurine treatment in inflammatory bowel disease.

Abstract：

BACKGROUND:Firm recommendations about the way thiopurine drugs are introduced and the use of thiopurine methyltransferase (TPMT) and metabolite measurements during treatment in inflammatory bowel disease (IBD) are lacking. AIM:To evaluate pharmacokinetics and tolerance after initiation of thiopurine treatment with a fixed dosing schedule in patients with IBD. PATIENTS:60 consecutive patients with Crohn's disease (n = 33) or ulcerative colitis (n = 27) were included in a 20 week open, prospective study. METHODS:Thiopurine treatment was introduced using a predefined dose escalation schedule, reaching a daily target dose at week 3 of 2.5 mg azathioprine or 1.25 mg 6-mercaptopurine per kg body weight. TPMT and ITPA genotypes, TPMT activity, TPMT gene expression, and thiopurine metabolites were determined. Clinical outcome and occurrence of adverse events were monitored. RESULTS:27 patients completed the study per protocol, while 33 were withdrawn (early protocol violation (n = 5), TPMT deficiency (n = 1), thiopurine related adverse events (n = 27)); 67% of patients with adverse events tolerated long term treatment on a lower dose (median 1.32 mg azathioprine/kg body weight). TPMT activity did not change during the 20 week course of the study but a significant decrease in TPMT gene expression was found (TPMT/huCYC ratio; p = 0.02). Patients with meTIMP concentrations >11,450 pmol/8 x 10(8) red blood cells during steady state at week 5 had an increased risk of developing myelotoxicity (odds ratio = 45.0; p = 0.015). CONCLUSIONS:After initiation of thiopurine treatment using a fixed dosing schedule, no general induction of TPMT enzyme activity occurred, though TPMT gene expression decreased. The development of different types of toxicity was unpredictable, but we found that measurement of meTIMP early in the steady state phase helped to identify patients at risk of developing myelotoxicity.

journal_name

Gut

journal_title

Gut

authors

Hindorf U,Lindqvist M,Peterson C,Söderkvist P,Ström M,Hjortswang H,Pousette A,Almer S

doi

10.1136/gut.2005.074930

keywords:

subject

Has Abstract

pub_date

2006-10-01 00:00:00

pages

1423-31

issue

eissn

0017-5749

issn

1468-3288

pii

gut.2005.074930

journal_volume

pub_type

杂志文章,多中心研究

在线工具

Pharmacogenetics during standardised initiation of thiopurine treatment in inflammatory bowel disease.