[The profile and clinical significance of azathioprine metabolic enzymes activity in rheumatological patients].
OBJECTIVE
To detect the activity of thiopurine methyltransferase (TPMT) and its relationship with azathioprine (AZA) tolerance.


METHODS
200 patients of rheumatism need AZA were included in the study. RBC TPMT activity was detected with high performance liquid chromatography. Then the patients took AZA doses of 50 mg/d for the first month, 100 mg/d for the second month and 150 mg/d for the third month.


RESULTS
TPMT activity of 200 patients ranged from 0.75 - 32.35 U/ml RBC, averaged (12.04 +/- 6.90) U/ml RBC. The activity of TPMT showed a normal skewness distribution and no activity deficiency was founded. 194 patients (97%) completed the 3 month follow-up. 18 showed bone marrow depression including 2 severe hematological crisis and 6 showed hepatic damage during the 3 months. Bone marrow depression was recorded of 7 cases with the TPMT activity of 2.24 - 5.97 U/ml RBC, averaged (3.47 +/- 1.21) U/ml RBC, among the dose of 50 mg/d and 11 cases with the TPMT activity of 4.01 - 11.17 U/ml RBC, averaged (7.08 +/- 2.58) U/ml RBC, among the dose of 100 - 150 mg/d. The other 176 cases did not show bone marrow depression at all, with TPMT activity of 4.47 - 32.35 U/ml RBC, averaged (13.02 +/- 6.07) U/ml RBC. TPMT activities in the 3 groups of patients were significantly different according to statistical analysis (P < 0.01).


CONCLUSIONS
Hematological side effects were highly associated with TPMT activity in AZA usage. Patients with low TPMT activity should use low dose of AZA routinely, even though, toxicity may occur. Test of TPMT activity before AZA description was of significance.
Zhan
Zhong-ping
ZP
Department of Rheumatology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
Yang
Xiu-yan
XY
Liang
Liu-qin
LQ
Wang
Yi-xi
YX
Huang
Min
M
Lian
Fan
F
D000293:Adolescent; D000328:Adult; D001379:Azathioprine / Q000009:adverse effects*; D001853:Bone Marrow / Q000187:drug effects; D004361:Drug Tolerance; D004912:Erythrocytes / Q000201:enzymology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D008297:Male; D008780:Methyltransferases / Q000378:metabolism*; D008875:Middle Aged; D012216:Rheumatic Diseases / Q000188:drug therapy / Q000201:enzymology*
D007166:Immunosuppressive Agents; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine