title: Allopurinol enhances the activity of hypoxanthine-guanine phosphoribosyltransferase in inflammatory bowel disease patients during low-dose thiopurine therapy: preliminary data of an ongoing series.
abstract: Thiopurines are crucial in the treatment of inflammatory bowel disease. The phenotype of pivotal metabolic enzymes determines whether thioguanine nucleotides (6-TGN) are generated in clinically sufficiently high levels. The first step in activation of thiopurine prodrugs to 6-TGN is catalysis by hypoxanthine-guanine phosphoribosyltransferase (HGPRT). Often, patients exhibit a clinically unfavorable metabolism, leading to discontinuation of conventional thiopurine therapy. The combination of allopurinol and low-dose thiopurine therapy may optimize this variant metabolism, presumably by affecting enzyme activities. We performed a prospective pharmacodynamic study to determine the effect of combination therapy on the activity of HGPRT. The activity of HGPRT and 6-TGN concentrations was measured in red blood cells during thiopurine monotherapy and after 4 weeks of combination therapy. The activity of HGPRT was also measured after 12 weeks of combination therapy. From the results, we conclude that combination therapy increases the activity of HGPRT and subsequently 6-TGN concentrations.
authors: Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands. ml.seinen@vumc.nl
authors: Margien L
authors: ML
authors: Seinen
authors: Nanne K H
authors: NK
authors: de Boer
authors: Kees
authors: K
authors: Smid
authors: Dirk P
authors: DP
authors: van Asseldonk
authors: Gerd
authors: G
authors: Bouma
authors: Adriaan A
authors: AA
authors: van Bodegraven
authors: Godefridus J
authors: GJ
authors: Peters
mesh_terms: D000293:Adolescent; D000328:Adult; D000493:Allopurinol / Q000008:administration & dosage / Q000627:therapeutic use*; D001379:Azathioprine / Q000627:therapeutic use; D002648:Child; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006074:Gout Suppressants / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000378:metabolism*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000201:enzymology*; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D008875:Middle Aged; D055815:Young Adult
chemical_list: D006074:Gout Suppressants; D000493:Allopurinol; C010240:6-methylthiopurine; D015122:Mercaptopurine; D007041:Hypoxanthine Phosphoribosyltransferase; D001379:Azathioprine