Zidovudine

The first agent available for treatment of HIV infection is the pyrimidine analog, 3’-azido-3’-deoxythymidine (AZT). to prevent prenatal infection in pregnancy. It is also used for prophylaxis in individuals exposed to HIV infection. The drug is well absorbed after oral administration. If taken with food, peak levels may be lower, but the total amount of drug absorbed is not affected. Penetration across the blood-brain barrier is excellent, and the drug has a half-life of 1 hour. The intracellular half-life, is approximately 3 hours. Most of the AZT is glucuronidated by the liver and then excreted in the urine. In spite of its seeming specificity, AZT is toxic to bone marrow. Headaches are also common. The toxicity of AZT is potentiated if glucuronidation is decreased by co-administration of drugs like probenecid, acetaminophen, lorazepam, indomethacin, and cimetidine. They should be avoided or used with caution in patients receiving AZT. Both stavudine and ribavirin are activated by the same intracellular pathways and should not be given with AZT.Dosage reduction is necessary in uremic patients and those with cirrhosis. The primary toxicity of zidovudine is bone marrow suppression (additive with other immunosuppressive drugs) leading to anemia and neutropenia, which may require transfusions. GI distress, thrombocytopenia, headaches, myalgia, acute cholestatic hepatitis, agitation, and insomnia may also occur. Drugs that may increase plasma levels of zidovudine include azole antifungals and protease inhibitors. Rifampin increases the clearance of zidovudine.