Abstract
The safe and effective use of cytotoxic drugs for debilitating and sometimes life-threatening dermatoses is of great interest. The thiopurine antimetabolite group of drugs that includes azathioprine, as well as 6-mercaptopurine and 6-thioguanine, have been widely used as immunosuppressant and steroid-sparing agents in a variety of cutaneous diseases. Numerous recent review articles have highlighted the potential for serious immunosuppression with these agents. l-6 However, there is a significant lack of information in the dermatologic literature concerning the important pharmacogenetic variations in thiopurine metabolism responsible for some cases of myelosuppression. During the past 15 years the genetic basis of variation in the activity of a key enzyme in thiopurine metabolism, thiopurine methyltransferase (TPMT), and its role in myelosuppression have been evaluated.7-10 Mounting evidence suggests that measurement of TPMT activity provides a rational basis for identifying enzyme-deficient patients at risk for profound myelosuppression, partially enzyme-deficient patients potentially at risk for myelosuppression, and perhaps even those with high enzyme activities who may be classified as therapeutic failures because of inadequate standard, empiric dosing with azathioprine and other thiopurine drugs. TPMT activity can be determined in peripheral red blood cell lysates, and this activity correlates with enzyme activity in the major drug metabolizing organ, the liver. 11’ l2 The clinical importance and utility of this
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.