Journal of Neurology and Neuro Toxicology

Abstract

Observations of Measurement of Thiopurine Metabolites to Monitor Response and Complications of Azathioprine Therapy in Neuromuscular Diseases

Author(s): Yu Zhao MD, Tulio E Bertorini MD

Azathioprine is an immunosuppressant, commonly used in autoimmune disorders. Due to its complex metabolism and genetic polymorphisms of metabolizing enzymes, there is wide variation in clinical response to standard dosage. We reviewed the records of 30 patients with neuromuscular disorders treated with Azathioprine. Thiopurine methyltransferase polymorphisms, thiopurine metabolites, CBC, and CMP were measured. The dosage of Azathioprine varied from 25 mg to 300 mg. The level of 6-thioguanine nucleotide ranged from 57 to 581 pmol/8 x 108 erythrocytes and 6-methylmercaptopurine from below 243 to 15,365 pmol/8 x 108 erythrocytes. In patients with normal or subtherapeutic metabolite levels, the dosage was increased when indicated, they showed improvement of symptoms, and when in toxic levels, the dosages were reduced. This study documents evidence of the usefulness of monitoring thiopurine metabolism particularly in patients at high risk, such as those taking drugs that decrease its metabolism, or increased dosages due to lack of response.

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