Table 12Effects of drugs on TPMT enzymatic activity

StudyDrug IDEffect on TPMT activity
Tinel
1991131
SKF 525-ANone
3,4-dimethoxy-5- hydroxybenzoic acidDecreased by 97%
Dewit
2002120
Acetylated metabolite of 5-aminosalicylic acid, with either sulfasalazine or mesalazine.No significant change after aminosalicylate withdrawal.
TPMT activity before withdrawal of aminosalicylate:
whole group: 12.29 U/mL RBCs (range 8.25±16.85);
sulfasalazine subgroup: 12.14 U/mL RBCs;
mesalazine subgroup 12.43 U/mL RBCs.
TPMT activity after aminosalicylate withdrawal:
whole group: 11.41 U/mL RBCs (7.3±14.5) (p=0.245, not significant);
sulfasalazine subgroup: 11.43 U/mL RBCs;
mesalazine subgroup: 11.39 U/mL RBCs.
Dilger
2007105
Azathioprine versus mesalazineNo significant differences between patients on azathioprine compared with those on mesalazine, at baseline or at any further visit.
Gisbert
2007104
5-aminosalycilatesNo differences between patients on azathioprine or 5- aminosalicylates versus controls.
Azathioprine: no treatment 20.7 U/mL RBCs versus treatment 21.2 U/mL RBCs
5-aminosalycilates: no treatment 20.9 U/mL RBCs versus treatment 21.2 U/mL RBCs
Dubinsky
2002119
MesalamineNo differences between patients on mesalamine medications versus controls (median 32.4 (range 14.7- 49.2) ELISA units vs. 31.8 (15.3–49.1 ELISA units)
Menor
2002117
azathioprineNo significant difference between patients on azathioprine versus no treatment
19.9 ± 6.0 U/mL RBCs versus 19.7±5.8 U/mL RBCs
Xin
2005102
sulfasalazine, 5-aminosalicylate, Ac-5-aminosalicylateNo significant effects in vitro.
IC50s:
Sulfasalazine: 9.4 (±3.1) μM
5-aminosalicylate: 236 (±55) μM
Ac-5-aminosalicylate: 73 (±20) μM
Jacqz- Aigrain
1994128
syringic acid, prednisone, prednisolone, 6- methylprednisolone, cyclophosphamide, methotrexate, trimethoprim sulphamethoxazoleNo significant effect in vitro.
Residual TPMT activity was always more than 70% of control activity.
Shipkova
2004114
sulfasalazineSignificant, concentration-dependent inhibition 11% for 80 μM to 45% for 640 μM sulfasalazine.
Brouwer,
2005110
methotrexate, trimethoprim, vincristine, dexamethasone, L-asparaginaseTPMT activity significantly increased in vitro.
2.4 μM trimethoprim: 148%
0.01 μM methotrexate: 147%.
Vincristine, dexamethasone and L-asparaginase had nonsignificant inhibitory effects on TPMT activity.

Abbreviations: IC50 = concentration of inhibitor at which enzyme activity is 50 percent of uninhibited activity; mL RBCs = milliliter of red blood cells; p = probability; TPMT = thiopurine methyltransferase; U = Unit = nanomole per hour; μM = micromoles per liter.

From: 3, Results

Cover of Assessment of Thiopurine Methyltransferase Activity in Patients Prescribed Azathioprine or Other Thiopurine-Based Drugs
Assessment of Thiopurine Methyltransferase Activity in Patients Prescribed Azathioprine or Other Thiopurine-Based Drugs.
Evidence Reports/Technology Assessments, No. 196.
Booth RA, Ansari MT, Tricco AC, et al.

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