thioguanine-anhydrous and Pemphigus

To prospectively determine optimal levels of 6-thioguanine nucleotide for disease remission in patients with immunobullous disease treated with azathioprine.. Prospective, longitudinal study. Laboratory tests and clinical evaluations were performed monthly for 6 months and then every 2 to 3 months (median follow-up, 13.4 months).. Tertiary care medical center.. Twenty-seven patients with immunobullous disease treated with azathioprine were enrolled during a 2-year period. Twelve met the criteria for evaluation of optimal levels of 6-thioguanine nucleotide.. Blood levels of 6-thioguanine nucleotide, 6-methylmercaptopurine, and thiopurine methyltransferase by polymerase chain reaction and enzyme activity were measured longitudinally during treatment.. The range of 6-thioguanine nucleotide was 48 to 457 pmol/8 x 10(8) red blood cells (RBCs), with an average optimal level of 190.7 pmol/8 x 10(8) RBCs for all patients. The mean optimal levels were 179.4 and 205.6 pmol/8 x 10(8) RBCs for pemphigus and pemphigoid, respectively. Limited disease required less 6-thioguanine, with a mean of 145.3 pmol/8 x 10(8) RBCs. Longitudinal induction of thiopurine methyltransferase activity was observed during treatment. Patients with recalcitrant disease showed higher induction of enzyme activity (with an increase of 9.1 to 23.6 U/mL of RBCs above baseline) than did those with responsive disease.. Optimal levels of 6-thioguanine nucleotide metabolites for disease remission in dermatology patients are 150 to 300 pmol/8 x 10(8) RBCs. High levels of the inactive metabolite 6-methylmercaptopurine and induction of thiopurine methyltransferase are associated with recalcitrant disease.

Topics: Adult; Aged; Aged, 80 and over; Azathioprine; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Longitudinal Studies; Male; Maximum Tolerated Dose; Methyltransferases; Middle Aged; Pemphigus; Polymerase Chain Reaction; Predictive Value of Tests; Prospective Studies; Risk Assessment; Severity of Illness Index; Thioguanine; Treatment Outcome

Azathioprine metabolism, to red cell 6-thioguanine nucleotides (6TGN), was studied in four patients with pemphigus vulgaris. Throughout treatment blood samples were taken for red cell 6TGN assay and differential white cell counts. Metabolite steady-state occurred in three patients in 2, 2 and 4 months respectively. In the fourth patient red cell 6TGN concentrations increased slowly over 3 years. There was a significant negative correlation between 6TGN concentrations and the white blood cell count (rs = -0.92, P less than 0.0005) in this patient.

Topics: Adult; Azathioprine; Female; Fluorescent Antibody Technique; Humans; Leukocyte Count; Male; Middle Aged; Pemphigus; Thioguanine