6-Mercaptopurine

Absorption

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.

Toxicity

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.

Chemical properties

Yellowish-Greenish Solid

Originator

Purinethol,Sandoz,France,1950

The Uses of 6-Mercaptopurine

Has a cytotoxicity effect

The Uses of 6-Mercaptopurine

6-Mercaptopurine (6-MP) is a antineoplastic, immonusupressant; inhibits purine nucleotide synthesis and metabolism. 6-MP have been used for several decades in the treatment of leukemia and certain other neoplastic diseases. 6-Mercaptopurine is used for maintenance therapy of acute lymphocytic and acute myelogenous leukemia.

Indications

For remission induction and maintenance therapy of acute lymphatic leukemia.

Background

An antimetabolite antineoplastic agent with immunosuppressant properties. It interferes with nucleic acid synthesis by inhibiting purine metabolism and is used, usually in combination with other drugs, in the treatment of or in remission maintenance programs for leukemia.

What are the applications of Application

6-Mercaptopurine is an inhibitor of de novo purine synthesis

Definition

A sulfurcontaining purine base not found in animal nucleoproteins.

Manufacturing Process

7.5 g of 4-amino-6-chloro-5-nitropyrimidine was suspended in 200 ml of 1 N potassium hydrosulfide and heated on the steam bath for 2 hours while passing hydrogen sulfide through the reaction mixture. The reaction mixture was allowed to cool slowly, acidified with 10 N sulfuric acid and chilled. The precipitate consisted of 4,5-diamino-6-mercaptopyrimidine and sulfur. It was boiled with 300 ml of water, filtered hot and then chilled. The product precipitated as pale yellow needles (4.2 g); an additional 0.95 g was obtained by concentration of the mother liquors to 100 ml.
A mixture of 2 g of 4,5-diamino-6-mercaptopyrimidine and 10 ml of 98% formic acid was heated at 70°C for two hours and then evaporated to dryness on the steam bath to give as a residue, 7-amino-thiazolo (5,4-d) pyrimidine.
To 820 mg of 7-amino-thiazolo[5,4-d]pyrimidine was added 2.5 cc of 2 N sodium hydroxide. The water was removed under reduced pressure. The sodium salt was then heated at 240°C for one hour, during which time it melted, gave off water and resolidified. The sodium salt of 6-mercaptopurine was dissolved in 15 ml of water and acidified to pH 5 with acetic acid. Yellow crystals of 6-mercaptopurine hydrate precipitated, according to US Patent 2,933,498.

brand name

Purinethol (Teva).

Therapeutic Function

Cancer chemotherapy

Hazard

Questionable carcinogen.

Pharmacokinetics

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.

Safety Profile

Poison by ingestion, intraperitoneal, subcutaneous, parenteral, and intravenous routes. Human systemic effects by ingestion: dermatitis. Experimental teratogenic and reproductive effects. Questionable human carcinogen producing Hodgkin's disease and leukemia. Human mutation data reported. When heated to decomposition it emits very toxic fumes of SOx and NOx. See also MERCAPTANS.

Veterinary Drugs and Treatments

Veterinary uses of mercaptopurine include adjunctive therapy of lymphosarcoma, acute leukemias, and severe rheumatoid arthritis. It may have potential benefit in treating other autoimmune conditions (e.g., unresponsive ulcerative colitis) as well.

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.