Clinical pharmacology of zidovudine and other 2',3'-dideoxynucleoside analogues.
Since the discovery of the acquired immunodeficiency syndrome (AIDS) in 1981, considerable progress has been made in the development of agents with anti-HIV activity. Zidovudine was one of the first 2'-3'-dideoxynucleosides to cause inhibition of human immunodeficiency virus (HIV) replication in vitro, by inhibiting the viral reverse transcriptase. Early trials showed that zidovudine results in clinical and immunological improvements and prolonged life in patients with AIDS or AIDS-related complex. However, haematological toxicity is the main drawback associated with zidovudine therapy. The initial recommended dose of zidovudine was 1500 mg per day, but recent studies have shown that dosages as low as 300 mg per day could be just as effective, without the severe haematological toxicity. Because zidovudine readily crosses the blood-brain barrier, it is used for the treatment of neurological diseases associated with HIV disease with some success. However, Kaposi's sarcoma does not respond to therapy with the drug. Apart from haematological toxicity, patients on long-term therapy with zidovudine may also develop resistance. Zidovudine use has also been associated with improvements in neurodevelopmental and growth velocity in HIV-infected children. The use of zidovudine as a prophylaxis has also been suggested, but the value of this is questionable. The combination of zidovudine with other agents, such as acyclovir and interferon, has a synergistic effect on the anti-HIV activity, with reduced drug toxicity. Other 2',3'-dideoxynucleoside analogues, such as dideoxycytidine (ddC) and dideoxyinosine (ddI) are effective anti-HIV agents and their use is also associated with both clinical and immunological improvements.(ABSTRACT TRUNCATED AT 250 WORDS)
Kamali
F
F
Wolfson Unit of Clinical Pharmacology, University of Newcastle upon Tyne.
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy; D000328:Adult; D002648:Child; D016049:Didanosine / Q000627:therapeutic use; D015224:Dideoxynucleosides / Q000494:pharmacology / Q000627:therapeutic use*; D004347:Drug Interactions; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D016602:Needlestick Injuries; D012514:Sarcoma, Kaposi / Q000188:drug therapy; D016047:Zalcitabine / Q000627:therapeutic use; D015215:Zidovudine / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
D015224:Dideoxynucleosides; D015215:Zidovudine; D016047:Zalcitabine; D007372:Interferons; D016049:Didanosine