2015 Antineoplastics

Pharmacokinetics

• given orally

• must be activated by HGPRT

6-MERCAPTOPURINE

• two metabolic pathways in liver:

  1. xanthine oxidase oxidizes 6-MP to 5-thiouric acid, which is inactive
     DOSE MUST BE ADJUSTED IF GIVEN WITH ALLOPURINOL (see TUMOUR LYSIS SYNDROME)

  2. 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

• Drug cards
• Nucleotide biochemistry
• Types
• Nucleotide synthesis inhibitors
  • Folic acid analogues
    • Mechanism of action
    • Resistance
    • Pharmacokinetics
    • Therapeutic Uses
    • Toxicity
    • Leucovorin rescue
  • Pyrimidine analogues
    • Mechanism of action
    • Resistance
    • Pharmacokinetics
    • Therapeutic Uses
    • Toxicity
  • Purine analogues
    • Review of purine synthesis
    • Mechanism of action
    • Resistance
    • Pharmacokinetics
    • Therapeutic Uses
    • Toxicity
    • Tumour lysis syndrome
• DNA synthesizing enzyme inhibitors