TY - JOUR
T1 - The continuous rediscovery and the benefit–risk ratio of thioguanine, a comprehensive review
AU - Bayoumy, Ahmed B.
AU - Simsek, Melek
AU - Seinen, Margien L.
AU - Mulder, Chris J.J.
AU - Ansari, Azhar
AU - Peters, Godefridus J.
AU - De Boer, Nanne K.
PY - 2020/2/1
Y1 - 2020/2/1
N2 - Introduction: In the 1950s, thioguanine (TG), a thiopurine-derivative together with azathioprine (AZA) and mercaptopurine (MP), were developed for the treatment of childhood leukemia. Over the years, the use of TG was also explored for other, mainly immune-mediated and inflammatory, diseases such as in the field of dermatology and rheumatology (e.g. psoriasis, systemic lupus erythematosus (SLE)) and gastroenterology and hepatology (e.g. inflammatory bowel diseases (IBD), autoimmune hepatitis). Areas covered: This review provides a comprehensive overview of all the clinical uses of TG and describes its mechanism of action, pharmacokinetic/pharmacodynamic features, and toxicity. Expert opinion: Thioguanine has shown beneficial clinical effects in hematological (particularly leukemia) and several immune-inflammatory diseases including psoriasis, SLE, polycythemia vera, Churg-Strauss syndrome, IBD, collagenous sprue, refractory celiac disease, and autoimmune hepatitis. Thioguanine is not effective in treating solid-cancers. At relatively low dosages, i.e. 0.2– 0.3mg/kg/day or 20 mg/day, TG has a favorable risk–benefit ratio and is a safe and effective drug in the long-term treatment of amongst other IBD patients. Thioguanine toxicity, especially myelotoxicity, and hepatotoxicity, including nodular regenerative hyperplasia (NRH) of the liver, is limited when dosed adequately. The occurrence of NRH appears dose-dependent and has been especially described during high dose TG above 40 mg/day.
AB - Introduction: In the 1950s, thioguanine (TG), a thiopurine-derivative together with azathioprine (AZA) and mercaptopurine (MP), were developed for the treatment of childhood leukemia. Over the years, the use of TG was also explored for other, mainly immune-mediated and inflammatory, diseases such as in the field of dermatology and rheumatology (e.g. psoriasis, systemic lupus erythematosus (SLE)) and gastroenterology and hepatology (e.g. inflammatory bowel diseases (IBD), autoimmune hepatitis). Areas covered: This review provides a comprehensive overview of all the clinical uses of TG and describes its mechanism of action, pharmacokinetic/pharmacodynamic features, and toxicity. Expert opinion: Thioguanine has shown beneficial clinical effects in hematological (particularly leukemia) and several immune-inflammatory diseases including psoriasis, SLE, polycythemia vera, Churg-Strauss syndrome, IBD, collagenous sprue, refractory celiac disease, and autoimmune hepatitis. Thioguanine is not effective in treating solid-cancers. At relatively low dosages, i.e. 0.2– 0.3mg/kg/day or 20 mg/day, TG has a favorable risk–benefit ratio and is a safe and effective drug in the long-term treatment of amongst other IBD patients. Thioguanine toxicity, especially myelotoxicity, and hepatotoxicity, including nodular regenerative hyperplasia (NRH) of the liver, is limited when dosed adequately. The occurrence of NRH appears dose-dependent and has been especially described during high dose TG above 40 mg/day.
KW - Thioguanine
KW - dermatology
KW - drug Rediscovery
KW - drug-induced liver injury
KW - gastroenterology
KW - hematology
KW - inflammatory Bowel Disease
KW - rheumatology
KW - thiopurines
UR - http://www.scopus.com/inward/record.url?scp=85081144846&partnerID=8YFLogxK
U2 - https://doi.org/10.1080/17425255.2020.1719996
DO - https://doi.org/10.1080/17425255.2020.1719996
M3 - Review article
C2 - 32090622
SN - 1742-5255
VL - 16
SP - 111
EP - 123
JO - Expert Opinion on Drug Metabolism & Toxicology
JF - Expert Opinion on Drug Metabolism & Toxicology
IS - 2
ER -