Limited intra-individual variability in hypoxanthine-Guanine phosphoribosyl transferase, thiopurine S-methyl transferase, and xanthine oxidase activity in inflammatory bowel disease patients during 6-thioguanine therapy.
6-Thioguanine (6-TG) may be indicated in case of intolerance of or resistance to conventional thiopurines in the treatment of inflammatory bowel diseases (IBD). The aim of our study was to evaluate the intrapatient variability in the 6-TG metabolizing enzymes: hypoxanthine-guanine phosphoribosyl transferase (HGPRT), thiopurine S-methyl transferase and xanthine oxidase. We performed a pharmacokinetic study of 6-TG after oral and intravenous administration in IBD patients in remission. The enzyme activities were determined at baseline and 1 week after the initiation of 6-TG in red blood cells, peripheral blood mononuclear cells (PBMC) or plasma. From the results we conclude that HGPRT activity in erythrocytes decreases following the initiation of 6-TG therapy, which may imply that HGPRT is a rate limiting enzyme in 6-TG metabolism. Moreover, little intrapatient variability in enzyme activities was observed except for HGPRT activity in PBMC. These data may have implications in regard of future therapeutic drug monitoring.
van Asseldonk
D P
DP
Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, the Netherlands. d.vanasseldonk@vumc.nl
de Boer
N K H
NK
Smid
K
K
Mulder
C J
CJ
van Bodegraven
A A
AA
Peters
G J
GJ
D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000201:enzymology*; D008297:Male; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D013866:Thioguanine / Q000378:metabolism / Q000627:therapeutic use*; D014969:Xanthine Oxidase / Q000235:genetics / Q000378:metabolism*
D000964:Antimetabolites, Antineoplastic; D014969:Xanthine Oxidase; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D007041:Hypoxanthine Phosphoribosyltransferase; D013866:Thioguanine