Combined antiviral effects of paired nucleosides against guinea pig cytomegalovirus replication in vitro

Liu, Yang; Crouch, Jill; Feng, Jingjing; Chou, Ting‐Chao; Hsiung, G. D.

doi:10.1016/0166-3542(90)90006-s

Cited by 9 publications

(6 citation statements)

References 41 publications

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“…In addition to th,ese observations with HIV-1, separate studies in our lab 7atory have shown that AZT antagonizes the anti-CMV ac4vity of GCV in vitro (24,27) and in vivo (9). Studies by ang et al (27) demonstrated that AZT reduced the potency of GCV ca.…”

supporting

confidence: 51%

See 1 more Smart Citation

Ganciclovir antagonizes the anti-human immunodeficiency virus type 1 activity of zidovudine and didanosine in vitro

Medina

Hsiung

Mellors

1992

Antimicrob Agents Chemother

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In studies examining potential interactions between ganciclovir (GCV) and either zidovudine (AZT) or didanosine (DDI) in H9 cells, GCV was found to consistently reduce the anti-human immunodeficiency virus type 1 potency of both AZT and DDI. In the presence of GCV, the 50% effective doses of AZT and DDI were increased three-to sixfold, depending on the molar ratio of drugs and the measure of human immunodeficiency virus type 1 replication (p24 antigen, reverse transcriptase activity, or infectious virus yield). Multiple dose-effect analysis revealed strong antagonism between GCV and either AZT or DDI (combination indices, 2.2 to 6.7). This antagonistic effect occurred at drug concentrations that were well below the cytotoxic range. At higher drug concentrations, the combination of GCV and AZT was synergistically cytotoxic (combination indices, <1.0), whereas GCV and DDI were only additively cytotoxic (combination indices, ca.

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supporting

confidence: 51%

“…Studies by ang et al (27) demonstrated that AZT reduced the potency of GCV ca. twofold against guinea pig CMV at GCV-to-AZT ratios of 1:0.8, 1:1.6, and 1:3.2.…”

mentioning

confidence: 99%

Ganciclovir antagonizes the anti-human immunodeficiency virus type 1 activity of zidovudine and didanosine in vitro

Medina

Hsiung

Mellors

1992

Antimicrob Agents Chemother

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“…In general, infected guinea pigs were more sensitive to drug toxicity than non-infected animals. Our previous study showed that at fixed ratios, AlT antagonizes the anti-CMV activity of DHPG in cultured cells (Yang et al, 1990). Similar results were obtained in Our present in vitro study using different fixed ratios.…”

Section: Effects Of Dhpg and Azt Each Stone Or In Combination On Bodysupporting

confidence: 91%

Zidovudine Antagonizes the Antiviral Effects of Ganciclovir against Cytomegalovirus Infection in Cultured Cells and in Guinea Pigs

Feng

Crouch

Tian

et al. 1993

Antivir Chem Chemother

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SummaryThe antiviral effects of gancicloyH (DHPG) combined with zidovudine (AZn at sevet~1 dosages against cytomegalovirus infection were evaluated in cultured cells and in Hartley guinea pigs. Combinations of DHPG and AZT at fixed ratios ranging from 1:0.1 to 1:1 showed reduced antiviral effects of DHPG in cultured human lung fibroblast (HEL) cells and guinea pig embryo (GPE) cells infected with human cytomegalovirus and guinea pig cyto'megalovirus, respectively.Synergistic cytotoxicity (CI values < 1) was noted in HEL and GPE cell cultures at all DHPG/AZT combinations tested. In vivo experiments using a fixed ratio at three dosage levels for treatment of GPCMV infected guinea pigs for 5 days did not show significant antagonistic antiviral nor synergistic toxic effects at lower dosages. When GPCMV infected guinea pigs were treated with DHPG and AZT in combinations at 40/20, 40/40 and 40/80 mg kg-1 day-1 for 7 days, a significant increase of GPCMV infectivity titres in the salivary gland, lung and spleen were noted when compared with those animals treated with DHPG 40mg kg-1 day-1 alone. In addition, histopathological findings showed more cytotoxicity in the bone marrow of infected and non-infected animals treated wth DHPGI AZT combinations than animals treated with each drug alone. These results suggest that AZT antagonizes the antiviral effects of DHPG against HCMV and GPCMV replication in cultured cells and GPCMV infection in guinea pigs with increased cytotoxicity in cultured cells and in bone marrow of animals receiving the drug combinations.

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“…Anti-HSV combinations: Schinazi et al (1986), in vitro and in vivo combinations; Gong et al (2004), betulin ϩ acyclovir. e. Anticytomegalovirus agent combinations: Yang et al (1990), two-drug combinations against COMPUTERIZED QUANTITATION OF SYNERGISM AND ANTAGONISM guinea pig cytomegalovirus in vitro. Manion et al (1996), two-drug combinations.…”

Section: B Examples Of Cited Applications In Drug Combinationsmentioning

confidence: 99%

Theoretical Basis, Experimental Design, and Computerized Simulation of Synergism and Antagonism in Drug Combination Studies

2006

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Combined antiviral effects of paired nucleosides against guinea pig cytomegalovirus replication in vitro

Cited by 9 publications

References 41 publications

Ganciclovir antagonizes the anti-human immunodeficiency virus type 1 activity of zidovudine and didanosine in vitro

Ganciclovir antagonizes the anti-human immunodeficiency virus type 1 activity of zidovudine and didanosine in vitro

Zidovudine Antagonizes the Antiviral Effects of Ganciclovir against Cytomegalovirus Infection in Cultured Cells and in Guinea Pigs

Theoretical Basis, Experimental Design, and Computerized Simulation of Synergism and Antagonism in Drug Combination Studies

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