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Pharmacology: Pharmacodynamics: Azathioprine mainly exhibits immunosuppressive activity. The exact mechanism of immunosuppressive activity of the drug has not been determined. The action of azathioprine probably depends on several factors. Azathioprine, which is an antagonist to purine metabolism, may inhibit RNA and DNA synthesis. The drug may also be incorporated into nucleic acids resulting in chromosome breaks, malfunctioning of the nucleic acids, or synthesis of fraudulent proteins. The drug may also inhibit coenzyme formation and function thereby interfering with cellular metabolism. Mitosis may also be inhibited by the drug.
Pharmacokinetics: Absorption: Azathioprine is readily absorbed from GI tract.
Distribution: Distribution of azathioprine has not been fully characterized, but the drug is rapidly cleared from blood. Both mercaptopurine and azathioprine are approximately 30% bound to serum proteins, but both appear to be dialyzable. Azathioprine and its metabolites have been shown to cross the placenta.
Metabolism: Azathioprine is metabolized in vivo to 6-mercaptopurine and a methylnitroimidazole moiety. The 6-MP easily passes cell membranes and is converted intracellularly into a number of thio-analogs of purines, amongst which the most important active nucleotide, 6-thioinosinic acid. The conversion rate varies from person to person. The formed 6-mercaptopurine is mainly excreted as the inactive (oxidized) metabolite thio-uric acid. This oxidation occurs through xanthine-oxidase. This enzyme is inhibited by allopurinol.
Elimination: The metabolites of azathioprine are excreted by the kidneys; only small amounts of azathioprine and mercaptopurine are excreted intact.
