Concise overview of the clinical pharmacokinetics of dideoxynucleoside antiretroviral agents

Burger, David M.; Meenhorst, Pieter L.; Beijnen, Jos H.

doi:10.1007/bf01875051

Cited by 15 publications

(3 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…d4T, ddC, ZDV and ddI were provided by Sigma (Taufkirchen, Germany). The drugs were used at concentrations close to their C max values: ZDV 1 µM [23], d4T 10 µM [24], ddI 10 µM [25] and ddC 0.2 µM [26].…”

Section: Cell Culture and Treatmentmentioning

confidence: 99%

Uridine Abrogates the Adverse Effects of Antiretroviral Pyrimidine Analogues on Adipose Cell Functions

Walker¹,

Auclair

Lebrecht³

et al. 2006

Antiviral Therapy

View full text Add to dashboard Cite

Objectives Side effects of antiretroviral treatment such as lipoatrophy have been mainly attributed to mitochondrial toxicity of nucleoside reverse transcriptase inhibitors (NRTIs). We assessed whether uridine can abrogate the adverse effects of NRTIs on adipocyte functions. Methods 3T3-F442A preadipocytes were exposed to stavudine (d4T; 10 μM), zidovudine (ZDV; 1 μM), zalcitabine (ddC; 0.2 μM) or didanosine (ddI; 10 μM) in the absence or presence of uridine 21 days prior to and 7 days after induction of differentiation. Then, lipid accumulation (oil red staining), apoptosis (flow cytometry, PARP-cleavage), mitochondrial mass (Mitotracker) and DNA (mtDNA), cytochrome c oxidase (COX) subunits and mitochondrial membrane potential (JC-1) were quantified. Results Whereas ddI had no effects, d4T, ZDV and ddC significantly decreased cellular lipid accumulation (by 32%, 46% and 24%, respectively), increased apoptosis and induced mitochondrial depolarization. d4T, ZDV and ddC decreased adipocyte mtDNA (by 64%, 53% and 46%, respectively) and reduced the mtDNA encoded COX II subunit. Uridine (200 μM) had no intrinsic effect, but prevented all adverse effects of d4T, ZDV and ddC on adipocyte morphology, lipid staining, apoptosis, mtDNA depletion (partial prevention with ZDV), mitochondrial mass and membrane potential. The effects of uridine were concentration-dependent. Uridine also fully reverted established d4T toxicities despite continued d4T exposure. Conclusions Uridine supplementation protects adipocytes from the adverse effects of d4T, ZDV and ddC on lipid accumulation, cell survival and mitochondrial functions, suggesting that the toxic effects could be linked to intracellular depletion of uridine or its metabolites. Uridine is an interesting candidate in the prevention of NRTI-induced lipoatrophy in vivo.

show abstract

Section: Cell Culture and Treatmentmentioning

confidence: 99%

Uridine Abrogates the Adverse Effects of Antiretroviral Pyrimidine Analogues on Adipose Cell Functions

Walker¹,

Auclair

Lebrecht³

et al. 2006

Antiviral Therapy

View full text Add to dashboard Cite

show abstract

“…Correlation exists between the onset of constitutional symptoms of AIDS and the level of CD 4 + T cells in HIV patients (Fauci et al 1985, Bacchetti andMoss 1989). Many studies have also demonstrated that this destruction of CD 4 + T cells population results in a critical immune deficiency that allows for the development of a wide range of opportunistic infections and tumors Fauci 1987, Mc Dougal andMoss 1985) Azidothymidine (AZT) is an antiretroviral drugs which inhibits HIV DNA replication in the CD 4 + T cells and thus has been used in the prophylactic treatment of AIDS symptoms (Sattentau, Claphan, & Weisis, 1988, Englund and Baker, 1997, Burger and Meenhorst, 1995andHammer, 1997. The therapeutic effectiveness of AZT was demonstrated in Caucasians whose AIDS disease is associated with HIV -1 (Yoffe and Fauci, 1987).…”

mentioning

confidence: 99%

Effect of Azidothymidine on CD4 Positive T Cells in HIV

Georgewill¹,

Ikimalo²

2005

Journal of Applied Sciences and Environmental Management

View full text Add to dashboard Cite

The effects of Azidothymidine (AZT) on the level of CD4 positive T cells in seropositive HIV patients regularly visiting the University Teaching Hospital, Port Harcourt and Braithwaite Memorial Hospital were selected for this investigation. Treatment group consisted of patients that received AZT at doses of 5mg/kg orally whereas the control group received placebo. The result shows that AZT increased significantly (P ≤ 0.01) CD4 + T cells level from 700 ± 3.00µl to 950±3.00µl while in the control group the significant decline (P≤ 0.01) of CD4 + T cells continued. This is indicative of the protective effects of AZT in preventing the destruction of CD4 + T cells by the HIV virus. The increased CD4 + T cells levels in the AZT treated patients was followed by concomitant reduction of the frequencies and severity of the HIV disease symptoms such as opportunistic infections and Lymphadenopathy. The control group had increase in the frequency and severity of these symptoms. The results of this study indicate that the use of AZT in the treatment of HIV positive patients is justified and therefore recommended especially in blacks. @JASEM

show abstract

“…The use of phenotypic assays to determinate drug susceptibilities of the patient's viral isolates in vitro, where available, limits the need to understand the relationships between viral genotypes and phenotypes, but may be misleading because the samples are not completely representative of the patient's entire viral population [11,12]. Furthermore, the concentrations of antiretroviral drugs used in vitro may not correlate with the concentrations of free and active drug in the body [13][14][15].…”

mentioning

confidence: 99%

Pharmacological Exposure and the Development of Drug Resistance in HIV

Hoetelmans

2001

Antiviral Therapy

View full text Add to dashboard Cite

Concise overview of the clinical pharmacokinetics of dideoxynucleoside antiretroviral agents

Cited by 15 publications

References 49 publications

Uridine Abrogates the Adverse Effects of Antiretroviral Pyrimidine Analogues on Adipose Cell Functions

Uridine Abrogates the Adverse Effects of Antiretroviral Pyrimidine Analogues on Adipose Cell Functions

Effect of Azidothymidine on CD4 Positive T Cells in HIV

Pharmacological Exposure and the Development of Drug Resistance in HIV

Contact Info

Product

Resources

About