zidovudine

Research Excerpts

Overview

Zidovudine (AZT) is an antiviral drug extensively used for combating the global pandemic- HIV/AIDS. It is a widely used component of antiretroviral therapy (ART) in resource-limited settings, despite its known adverse effects, which include mitochondrial toxicity in muscle, liver and adipose tissue.

Effects

Zidovudine is an effective antiretroviral treatment in adults with human immunodeficiency virus (HIV) infection. It has been associated with 'ragged-red' fibre myopathy, due to its effects on myocyte mitochondria.

Actions

Zidovudine (AZT) may produce a good platelet increase in a large number of patients. There is no consensus for the use of this anti-retroviral drug in otherwise asymptomatic HIV-positive patients.

Treatment

Zidovudine treatment, cirrhosis, baseline low body weight, use of PEG-IFN-alpha2a, and baseline haemoglobin level < 14 g/dl are predictors of overall severe haematological toxicity. Treatment with ZDV at 1 mg/ml delayed disease progression if started 24 h prior to inoculation.

Toxicity

Zidovudine appears to be safe in subjects with HAM who have no other major health problems and should be investigated further. The major adverse effect of ZDV is haematological toxicity which results in anaemia and granulocytopenia.

Pharmacokinetics

The pharmacokinetic profile of oral zidovudine entrapped in a 50:50 polyactide-coglycolide matrix (nanospheres) was compared to those of standard oral and parenteral zidvudine formulations in rabbits. The objective of this in silico study is to elucidate the pharmacokinetics origins of the drug.

Compound-Compound Interactions

The safety, pharmacokinetics, and antiretroviral activity of lamivudine alone and in combination with zidovudine was studied in pregnant women infected with human immunodeficiency virus type 1 (HIV-1) and their neonates. The authors studied the effect of zidvudine (ZDV) resistance mutation on virologic response to treatment with ZDV or stavudine.

Bioavailability

The basic pharmacokinetic and bioavailability information on zidovudine was obtained during the initial phase I study. The relative bioavailability of zidvudine-loaded PLA-PEG blend nanoparticles was 2. Since the bioavailability is not particularly impaired, oral zidavudine therapy can be maintained in patients with diarrhoea.

Dosage Studied

Zidovudine (AZT) is commonly used to treat patients with AIDS, but it is limited by toxicity and high dosing needs. In single dose acute toxicity studies in CD-1 mice and CD rats, the median lethal dose (MLD) was > 750 mg/kg after iv dosing and > 3000 mg/ kg after po administration.