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Thiopurine S-methyltransferase as a target for drug interactions.

Abstract：

OBJECTIVE:The present study was undertaken to investigate the possible effects of various agents on thiopurine methyltransferase (TPMT) activity in red blood cells (RBCs) from patients with chronic inflammatory bowel disease (IBD). METHODS:In three groups of patients with very high, normal and intermediate TPMT activity (each n=6), the inhibitory potential of furosemide, piretanide, azathioprine (AZA) and testosterone was assessed by ex vivo measurements of TPMT activity in RBCs. From individual concentration-response curves, IC50 values have been determined. RESULTS:Independent of the basal TPMT activity, lowest IC50 values were calculated for furosemide (15-19 microM), followed by testosterone (30-72 microM), piretanide (300-313 microM) and AZA (430-532 microM). Compared with reported plasma concentration achieved during treatment, only furosemide would have the potential to inhibit TPMT also in vivo, whereas the IC50 values of the other agents are far above the corresponding plasma levels. CONCLUSIONS:Our ex vivo study revealed that only furosemide has the potential to inhibit TPMT activity in patients with IBD. This possibility should be taken into consideration if the diuretic and AZA or 6-mercaptopurine are coadministered. However, the extrapolation to the clinical setting remains open.

journal_name

Eur J Clin Pharmacol

journal_title

European journal of clinical pharmacology

authors

Xin HW,Fischer C,Schwab M,Klotz U

doi

10.1007/s00228-005-0950-5

subject

Has Abstract

pub_date

2005-07-01 00:00:00

pages

395-8

issue

5-6

eissn

0031-6970

issn

1432-1041

journal_volume

61

pub_type

杂志文章

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