MERCAPTOPURINE

Chemistry - A purine analog, mercaptopurine occurs as a slightly yellow, crystalline powder. It isinsoluble in water and has a pKa of 7.6. Mercaptopurine may also be known as 6-mercaptopurineor 6-MP.

Storage, Stability, Compatibility

Mercaptopurine tablets should be stored at room temperaturein well-closed containers.

Pharmacology - MERCAPTOPURINE

Intracellularly, mercaptopurine is converted into a ribonucleotide which acts as apurine antagonist, thereby inhibiting RNA and DNA synthesis. Mercaptopurine also acts as animmunosuppressant, primarily inhibiting humoral immunity.

Uses, Indications

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

Pharmacokinetics - MERCAPTOPURINE

Absorption after oral dosing is variable and incomplete. Absorbed drug andits metabolites are distributed throughout the total body water. The drug crosses the blood-brainbarrier, but not in levels significant enough to treat CNS neoplasms. It is unknown whether mercaptopurine enters milk.
Via the enzyme, xanthine oxidase, mercaptopurine is rapidly metabolized in the liver to 6-thiouricacid, which along with the parent compound and other metabolites are principally excreted in theurine.

Contraindications, Precautions, Reproductive Safety

Mercaptopurine is contraindicated inpatients hypersensitive to it. The drug should be used cautiously (risk versus benefit) in patientswith hepatic dysfunction, bone marrow depression, infection, renal function impairment (adjustdosage) or have a history of urate urinary stones.
Mercaptopurine is mutagenic and teratogenic and is not recommended for use during pregnancy.
Use of milk replacer is recommended for nursing bitches or queens.

Adverse Effects, Warnings

At usual doses, GI effects (nausea, anorexia, vomiting, diarrhea) aremost likely seen in small animals. However, bone marrow suppression, hepatotoxicity, pancreatitis,
GI (including oral) ulceration, and dermatologic reactions are potentially possible.
Overdosage, Acute Toxicity - Toxicity may present acutely (GI effects) or be delayed (bonemarrow depression, hepatotoxicity, gastroenteritis). It is suggested to use standard protocols toempty the GI tract if ingestion was recent and to treat supportively.

Drug Interactions

The hepatic metabolism of mercaptopurine may be decreased by concomitantadministration of allopurinol. In humans, it is recommended to reduce the mercaptopurine dose to1/4-1/3 usual if both drugs are to used together.
Use extreme caution when used concurrently with other drugs that are also myelosuppressive, including many of the other antineoplastics and other bone marrow depressant drugs (e.g., chloramphenicol, flucytosine, amphotericin B, or colchicine). Bone marrow depression maybe additive. In humans, enhanced bone marrow depression has occurred when used concomitantlywith trimethoprim/sulfa. Use with other immunosuppressant drugs (e.g., azathioprine, cyclophosphamide, corticosteroids) may increase the risk of infection. Live virus vaccinesshould be used with caution, if at all during therapy.
Mercaptopurine should be used cautiously with other drugs that can cause hepatotoxicity (e.g., halothane, ketoconazole, valproic acid, phenobarbital, primidone, etc.). In humans, one studydemonstrated increased hepatotoxicity when mercaptopurine was used in conjunction with doxorubicin.
Laboratory Considerations - Mercaptopurine may give falsely elevated serum glucose and uricacid values when using a SMA (sequential multiple analyzer) 12/60.