High 6-thioguanine nucleotide levels and low thiopurine methyltransferase activity in patients with lupus erythematosus treated with azathioprine

American Journal of Therapeutics
G DecauxJ P Desager

Abstract

Azathioprine (AZA) is characterized by a high interindividual variability in bioavailability and metabolism. AZA is converted into 6-thioguanine nucleotides (6-TGN) to which the immune modifier activity is attributed. The 6-TGN levels are known to be affected by the activity of the key enzyme, thiopurine methyltransferase (TPMT), which is under genetic dependence. The authors measured a significantly lower TPMT activity in 53 women with systemic lupus erythematosus (SLE) (12.2 +/- 2.4 pmol/h/ml RBC; P < 0.01) when compared with 30 healthy control participants (13.15 +/- 3.1 pmol/h/ml RBC) but not with 28 patients with other dysimmune diseases (non-SLE; 13.0 +/- 3.0 pmol/h/ml RBC; P = 0.10). To evaluate the impact of TPMT activity on the concentrations of AZA metabolites, we measured the TPMT activity and 6-TGN levels in a subgroup of 26 patients in remission and treated with a stable dose of AZA (mean value: 1.9 +/- 0.5 mg/kg/day) for at least six months (n = 13 with SLE and n = 13 with other dysimmune diseases, ie, non-SLE). In such a subgroup, no correlation between 6-TGN levels and TPMT activity was observed. However, patients with SLE presented lower TPMT activity and higher 6-TGN levels (215 +/- 123 versus 140 +/- 75 pmol/...Continue Reading

References

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Nov 1, 1993·Scandinavian Journal of Clinical and Laboratory Investigation·B KlemetsdalJ Aarbakke
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Mar 11, 2000·The Journal of Laboratory and Clinical Medicine·G DecauxJ P Desager

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Citations

Mar 6, 2007·Digestive Diseases and Sciences·Javier P GisbertLuis G Guijarro
Nov 8, 2005·Biological & Pharmaceutical Bulletin·Yuko OkadaKoujirou Yamamoto
Oct 30, 2010·Seminars in Arthritis and Rheumatism·Gabriela Schmajuk, Jinoos Yazdany
Feb 10, 2009·Gastroentérologie Clinique Et Biologique·X RoblinL Peyrin-Biroulet
Mar 13, 2014·International Journal of Rheumatic Diseases·Antony B FriedmanPeter R Gibson
Apr 18, 2015·International Journal of Rheumatic Diseases·Lucy Croyle, Eric F Morand
Dec 26, 2016·Rheumatology·Diane Apostolopoulos, Eric F Morand
Jul 18, 2002·Multiple Sclerosis : Clinical and Laboratory Research·C MenorL G Guijarro

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