Pharmacokinetics and Immune Reconstitution Following Discontinuation of Thiopurine Analogues: Implications for Drug Withdrawal Strategies.

摘要: Background and aims Discontinuation of thiopurine analogues is common prior to live vaccines, during infection or when de-escalating therapy. Data regarding clearance active metabolites immune re-constitution scant. We aimed determine drug elimination following cessation. Methods The kinetics 6-thioguanine nucleotides (6-TGN) were determined in nine inflammatory bowel disease [IBD] patients discontinuing thiopurines. Immune reconstitution was evaluated by toxic shock syndrome toxin 1 [TSST1] anti-CD3 [OKT3]-induced CD4+ T-cell proliferation, an initial exposure TSST1 6-mercaptopurine [6MP], separately combined. Results All thiopurines displayed first-order 6-TGN, with a median half-life 6.8 days [interquartile range 5.9-8.4]. Resting T-cells exposed 6MP preserved their response subsequent polyclonal Vβ2+-preferential stimulation. By contrast, TSST1-activated inhibited Vβ2+clonal further stimulation [p = 0.008], whereas overall non-Vβ2-selective OKT3 unaltered 0.9]. Conclusions Upon 6MP/azathioprine discontinuation, 6-TGN less than 10 expected most patients. reconstitution, however, may take longer for clones treatment. These findings be useful considering