Brands, Medical Use, Clinical Data
- Antineoplastic Agents
- Purine analogues
- Tablet (50-mg, scored) for oral administration
Brands / Synonyms
6 MP; Ismipur; Leukeran; Leukerin; Leupurin; Mercaleukim; Mercaleukin; Mercaptopurine; Mercaptopurine Monohydrate; Mercapurin; Mern; MP; Puri-Nethol; Purimethol; Purinethol; Purinethol
For remission induction and maintenance therapy of acute lymphatic leukemia.
Mercaptopurine is one of a large series of purine analogues which interfere with nucleic acid biosynthesis and has been found active against human leukemias. It is an analogue of the purine bases adenine and hypoxanthine. It is not known exactly which of any one or more of the biochemical effects of mercaptopurine and its metabolites are directly or predominantly responsible for cell death.
Mechanism of Action
Mercaptopurine 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).
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.
Biotrnasformation / Drug Metabolism
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.
PURINETHOL should not be used unless a diagnosis of acute lymphatic leukemia has been adequately
established and the responsible physician is knowledgeable in assessing response to chemotherapy.
PURINETHOL should not be used in patients whose disease has demonstrated prior resistance to this
drug. In animals and humans, there is usually complete cross-resistance between mercaptopurine and thioguanine.
PURINETHOL should not be used in patients who have a hypersensitivity to mercaptopurine or any
component of the formulation.
When allopurinol and mercaptopurine are administered concomitantly, it is imperative that the dose of
mercaptopurine be reduced to one third to one quarter of the usual dose. Failure to observe this dosage reduction
will result in a delayed catabolism of mercaptopurine and the strong likelihood of inducing severe toxicity.
There is usually complete cross-resistance between mercaptopurine and thioguanine.
The dosage of mercaptopurine may need to be reduced when this agent is combined with other drugs whose
primary or secondary toxicity is myelosuppression. Enhanced marrow suppression has been noted in some patients also
Inhibition of the anticoagulant effect of warfarin, when given with mercaptopurine, has been
As there is in vitro evidence that aminosalicylate derivatives (e.g., olsalazine, mesalazine, or
sulphasalazine) inhibit the TPMT enzyme, they should be administered with caution to patients receiving concurrent