TY - JOUR
T1 - Sulphasalazine inhibition of thiopurine methyltransferase
T2 - possible mechanism for interaction with 6‐mercaptopurine and azathioprine.
AU - Szumlanski, CL
AU - Weinshilboum, RM
PY - 1995/4
Y1 - 1995/4
N2 - Thiopurine drugs are used in the treatment of inflammatory bowel disease—as are sulphasalazine and its metabolite 5‐aminosalicylic acid (ASA). S‐Methylation catalyzed by thiopurine methyltransferase (TPMT) is a major pathway in the metabolism of thiopurines. The hypothesis was tested that TPMT might be inhibited by sulphasalazine or isomers of ASA. Sulphasalazine as well as 3‐, 4‐ and 5‐ASA inhibited recombinant human TPMT, with IC50 values of 78, 99, 2600 and 1240 microM, respectively. Kinetic studies demonstrated that the inhibition of TPMT by sulphasalazine and ASA isomers was non‐competitive with regard to the thiopurine substrate, 6‐MP, and was uncompetitive with regard to the methyl donor for the reaction, S‐adenosyl‐L‐methionine. Our observations raise the possibility of a clinically significant drug‐ drug interaction in patients treated simultaneously with sulphasalazine and thiopurine drugs. 1995 The British Pharmacological Society
AB - Thiopurine drugs are used in the treatment of inflammatory bowel disease—as are sulphasalazine and its metabolite 5‐aminosalicylic acid (ASA). S‐Methylation catalyzed by thiopurine methyltransferase (TPMT) is a major pathway in the metabolism of thiopurines. The hypothesis was tested that TPMT might be inhibited by sulphasalazine or isomers of ASA. Sulphasalazine as well as 3‐, 4‐ and 5‐ASA inhibited recombinant human TPMT, with IC50 values of 78, 99, 2600 and 1240 microM, respectively. Kinetic studies demonstrated that the inhibition of TPMT by sulphasalazine and ASA isomers was non‐competitive with regard to the thiopurine substrate, 6‐MP, and was uncompetitive with regard to the methyl donor for the reaction, S‐adenosyl‐L‐methionine. Our observations raise the possibility of a clinically significant drug‐ drug interaction in patients treated simultaneously with sulphasalazine and thiopurine drugs. 1995 The British Pharmacological Society
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U2 - 10.1111/j.1365-2125.1995.tb04478.x
DO - 10.1111/j.1365-2125.1995.tb04478.x
M3 - Article
C2 - 7640156
AN - SCOPUS:0028917479
SN - 0306-5251
VL - 39
SP - 456
EP - 459
JO - British Journal of Clinical Pharmacology
JF - British Journal of Clinical Pharmacology
IS - 4
ER -