Archives of dermatology · 2009
Thioguanine nucleotides and thiopurine methyltransferase in immunobullous diseases: optimal levels as adjunctive tools for azathioprine monitoring.
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el-Azhary Rokea A, Farmer Sara A, Drage Lisa A, Rogers Roy S, McEvoy Marian T, Davis Mark D P, Bridges Alina G, Gibson Lawrence E
Аннотация
OBJECTIVE: To prospectively determine optimal levels of 6-thioguanine nucleotide for disease remission in patients with immunobullous disease treated with azathioprine.
DESIGN: 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).
SETTING: Tertiary care medical center.
PATIENTS: 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.
MAIN OUTCOME MEASURES: Blood levels of 6-thioguanine nucleotide, 6-methylmercaptopurine, and thiopurine methyltransferase by polymerase chain reaction and enzyme activity were measured longitudinally during treatment.
RESULTS: 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.
CONCLUSIONS: 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.
DESIGN: 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).
SETTING: Tertiary care medical center.
PATIENTS: 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.
MAIN OUTCOME MEASURES: Blood levels of 6-thioguanine nucleotide, 6-methylmercaptopurine, and thiopurine methyltransferase by polymerase chain reaction and enzyme activity were measured longitudinally during treatment.
RESULTS: 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.
CONCLUSIONS: 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.
Предметные рубрики MeSH
AdultAgedAged, 80 and overAzathioprineDose-Response Relationship, DrugDrug Administration ScheduleFemaleFollow-Up StudiesHumansLongitudinal StudiesMaleMaximum Tolerated DoseMethyltransferasesMiddle AgedPemphigusPolymerase Chain ReactionPredictive Value of TestsProspective StudiesRisk AssessmentSeverity of Illness IndexThioguanineTreatment Outcome