Zidovudine (3-azido-3'-deoxythymidine), also referred to as azidothymidine (AZT), has become an integral component in highly active antiretroviral therapy, and has also been used in the treatment of cancer. The clinical effectiveness of AZT is constrained due to its association with increased adverse effects, such as myopathy. There are numerous potential mechanisms that may contribute to AZT-i...

The alveolar macrophage (AM), as a representative human tissue macrophage, was used in an in vitro system to examine the anti-human immunodeficiency virus type-1 (HIV-1) activity of zidovudine (AZT) and granulocytemacrophage colony-stimulating factor (GM-CSF). AMs were infected with the lllB strain of HIV-1 and exposed to AZT (1 pmol/L), GM-CSF (30 U/mL), a combination of AZT (1 pmol/L)/GM-CSF ...

BACKGROUND We previously demonstrated in vitro that zidovudine (AZT) selects for A371V in the connection domain and Q509L in ribonuclease H (RNase H) domain of HIV-1 reverse transcriptase (RT) which, together with the thymidine analog mutations D67N, K70R and T215F, confer greater than 100-fold AZT resistance. The goal of the current study was to determine whether AZT monotherapy in HIV-1 infec...

Herb-drug interaction related with the drugs used to treat HIV patients was speculated in the present study. Therefore, zidovudine (AZT) was selected as an example, and in vitro incubation model was utilized to evaluate the inhibitory effect of herbal component methylophiopogonanone A towards the metabolism of AZT. The results showed the concentration-dependent inhibition of methylophiopogonano...

5'-O-Dipeptide ester prodrugs of antiviral zidovudine (AZT) were designed to target the human intestinal oligopeptide transporter, hPEPT1, and were evaluated for their stability at pH 7.4 in buffer and in human plasma, affinity toward hPEPT1, cytotoxicity, and antiretroviral activity. The dipeptide esters of AZT undergo cyclization in buffer at pH 7.4 to release the parent drug at a rate that d...

BACKGROUND Humans can be frequently exposed to Bisphenol A (BPA) via multiple sources, and babies are considered to be the most sensitive group to exposure of BPA. AIMS To investigate the inhibition potential of BPA towards human liver microsomes (HLMs)-catalyzed zidovudine (AZT) glucuronidation. MATERIALS AND METHODS In vitro HLMs incubation system was used to investigate the inhibition po...

The purpose of this study was to determine if a correlation exists between long-term azidothymidine (AZT) therapy and low pseudocholinesterase concentrations in patients who are infected with the human immunodeficiency virus (HIV). A pilot study was conducted of 10 patients infected with HIV, 5 of whom were receiving AZT. Laboratory tests, including complete blood count (CBC), liver function te...

In a model system employing Chinese hamster V-79 cells, the DNA synthesis inhibitor 3'-azido-3'-deoxythymidine (BW A509U, AZT) was shown to induce genome-wide DNA hypermethylation, low-frequency silencing of thymidine kinase (TK; EC 2.7.1.21) gene expression, and resistance to AZT. Twenty-four hours of exposure of V-79 cells to 150 microM AZT led to > 2-fold enhancement of genomic 5-methylcytos...

3'-Azido-3'-deoxythymidine (AZT) is frequently prescribed to patients infected with the human immunodeficiency virus. After absorption, AZT is rapidly metabolized into 3'-azido-3'-deoxy-5'-glucuronylthymidine by UDP-glucuronosyltransferase (UGT) enzymes. Using labeled [(14)C]UDP-glucuronic acid and microsomal preparations from human kidney 293 cells stably expressing the different human UGT2B i...