For remission induction and maintenance therapy of acute lymphatic leukemia.
Purinethol Mechanism Of Action:
Purinethol competes with hypoxanthine and guanine for the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) and is itself converted to thioinosinic acid (TIMP). This intracellular nucleotide inhibits several reactions involving inosinic acid (IMP), including the conversion of IMP to xanthylic acid (XMP) and the conversion of IMP to adenylic acid (AMP) via adenylosuccinate (SAMP). In addition, 6-methylthioinosinate (MTIMP) is formed by the methylation of TIMP. Both TIMP and MTIMP have been reported to inhibit glutamine-5-phosphoribosylpyrophosphate amidotransferase, the first enzyme unique to the de novo pathway for purine ribonucleotide synthesis. Experiments indicate that radiolabeled mercaptopurine may be recovered from the DNA in the form of deoxythioguanosine. Some mercaptopurine is converted to nucleotide derivatives of 6-thioguanine (6-TG) by the sequential actions of inosinate (IMP) dehydrogenase and xanthylate (XMP) aminase, converting TIMP to thioguanylic acid (TGMP).
Purinethol Drug Interactions:
Allopurinol Allopurinol increases the effect of thiopurine
Anisindione The thiopurine decreases the anticoagulant effect
Acenocoumarol The thiopurine decreases the anticoagulant effect
Dicumarol The thiopurine decreases the anticoagulant effect
Warfarin The thiopurine decreases the anticoagulant effect
Atracurium The agent dereases the effect of the muscle relaxant
Doxacurium The agent dereases the effect of the muscle relaxant
Gallamine Triethiodide The agent dereases the effect of the muscle relaxant
Metocurine The agent dereases the effect of the muscle relaxant
Mivacurium The agent dereases the effect of the muscle relaxant
Pancuronium The agent dereases the effect of the muscle relaxant
Tubocurarine The agent dereases the effect of the muscle relaxant
Vecuronium The agent dereases the effect of the muscle relaxant
Olsalazine The 5-ASA derivative increases the toxicity of thiopurine
Sulfasalazine The 5-ASA derivative increases the toxicity of thiopurine
Mesalazine The 5-ASA derivative increases the toxicity of thiopurine
Clinical studies have shown that the absorption of an oral dose of mercaptopurine in humans is incomplete and variable, averaging approximately 50% of the administered dose. The factors influencing absorption are unknown.
Signs and symptoms of overdosage may be immediate such as anorexia, nausea, vomiting, and diarrhea; or delayed such as myelosuppression, liver dysfunction, and gastroenteritis. The oral LD50 of mercaptopurine was determined to be 480 mg/kg in the mouse and 425 mg/kg in the rat.
Hepatic. Degradation primarily by xanthine oxidase. The catabolism of mercaptopurine and its metabolites is complex. In humans, after oral administration of 35S-6-mercaptopurine, urine contains intact mercaptopurine, thiouric acid (formed by direct oxidation by xanthine oxidase, probably via 6-mercapto-8-hydroxypurine), and a number of 6-methylated thiopurines. The methylthiopurines yield appreciable amounts of inorganic sulfate.