Jornal Brasileiro de Patologia e Medicina Laboratorial
On-line version ISSN 1678-4774
PACHECO NETO, Maurílio et al. Therapeutic drug monitoring of azathioprine: a review. J. Bras. Patol. Med. Lab. [online]. 2008, vol.44, n.3, pp. 161-167. ISSN 1678-4774. http://dx.doi.org/10.1590/S1676-24442008000300002.
Thioguanine nucleotides (6-TGN), active metabolites of azathioprine (AZA) and 6-mercaptopurine (6-MP), act as purine antagonists, inhibiting DNA, RNA, and protein synthesis and inducing cytotoxicity and immunosuppression. The genetically determined thiopurine methyltransferase enzyme (TPMT) is involved in the metabolism of these agents and, theoretically, determines the clinical response to thiopurines. Low activity of this enzyme decreases the methylation of thiopurines, what results in potential overdosing, whereas high TPMT status leads to overproduction of toxic metabolite 6-methilmercaptopurine (6-MMP) and ineffectiveness of AZA and 6-MP. Several mutations in the TPMT gene have been identified and correlated with low activity phenotypes. In this study, we also discuss the therapeutic monitoring of these drugs by means of red blood cell 6-TGN levels, which correlate with immunosuppression and mielotoxicity. 6-MMP is directly connected with hepatotoxicity. These metabolites assays are associated with the use of appropriate doses of this drug, what results in a better control of the disease and a decreased use of corticosteroids.
Keywords : 6-mercaptopurine; 6-thioguanine; Azathioprine; Drug monitoring; Immunosuppression; Liquid chromatography.