C. PURINE ANALOGUES : 6-MERCAPTOPURINE (6-MP), 6-THIOGUANINE (6-TG)
Pharmacokinetics
-
given orally
- must be activated by HGPRT
6-MERCAPTOPURINE
- two metabolic pathways in liver:
-
xanthine oxidase oxidizes 6-MP to 5-thiouric acid, which is inactive
DOSE MUST BE ADJUSTED IF GIVEN WITH ALLOPURINOL (see TUMOUR LYSIS SYNDROME) - methylation and subsequent oxidation
- the enzyme responsible (thiopurine methyltransferase) has no known natural function, and polymorphic inheritance; 15% of the UK population has little or no enzyme activity, which causes increased toxicity
-
6-THIOGUANINE
- unlike 6-MP, 6-TG can be administered concurrently with ALLOPURINOL