Drug Breakdown: Mercaptopurine

Day 1: A metabolite of azathioprine, #mercaptopurine was discovered to be an immunosuppressant circa 1950s. The role for #mercaptopurine developed in leukaemias (acute and maintenance therapy) and inflammatory bowel disease (IBD) for maintenance of remission for Crohn's disease and ulcerative colitis (IBD unlicensed role).

(cont) Dose; significant individual variations in kinetics such as drug metabolism, and in dynamics such as intracellular uptake and breakdown, mean an individual approach. Adult acute chemotherapy 2.5-5 mg/kg PO once daily, maintenance 1.5-2.5 mg/kg/day. IBD 1-1.5 mg/kg; British National Formulary states lower can be effective e.g some IBD sites state 0.75-1.5 mg/kg/day. Use unlicensed in children, chemotherapy dose customised, IBD as per adult.

Day 2: #mercaptopurine is a purine analogue, which competes with purines for enzymatic breakdown at multiple stages, interfering with nucleic acid synthesis. Acting as a purine decoy impairs DNA formation with toxic breakdown products, leading to cell death.

(cont) Rapidly dividing cells such as tumours and bone marrow blood cells are most affected, some of which control inflammation. When used in inflammatory bowel conditions, the effects/full effects may not be experienced for three, or even six months.