Three-dimensional Analysis of the Synergistic Cytotoxicity of Ganciclovir and Zidovudine

Overview

Journal Antimicrob Agents Chemother

Publisher American Society for Microbiology

Specialty Pharmacology

Date 1991 Jun 11

PMID 1929243

Citations 28

Authors

M N Prichard

L E PRICHARD

W A Baguley

M R Nassiri

C Shipman Jr

Affiliations

Soon will be listed here.

Abstract

The combined cytotoxicity of zidovudine and ganciclovir in three cell lines of human origin was examined. The data were generated by a new rapid cell proliferation assay and a more sensitive plating efficiency assay. A three-dimensional analytical approach was used to evaluate the drug-drug interactions, and the results were compared with those obtained by two conventional methods of analysis. Synergistic cytotoxicity was observed in all cell lines examined and by both assays. Moreover, this synergistic cytotoxicity was statistically significant at physiologically relevant concentrations. It is not known whether these drug-drug interactions manifest themselves in vivo as granulocytopenia or other untoward side effects. These results, however, indicate that further investigation is warranted and that the coadministration of zidovudine and ganciclovir may be contraindicated.

Citing Articles

Structural and Synthetic Aspects of Small Ring Oxa- and Aza-Heterocyclic Ring Systems as Antiviral Activities.

Manna S, Das K, Santra S, Nosova E, Zyryanov G, Halder S Viruses. 2023; 15(9).

PMID: 37766233 PMC: 10536032. DOI: 10.3390/v15091826.

Integrin αvβ3 Is a Master Regulator of Resistance to TKI-Induced Ferroptosis in HER2-Positive Breast Cancer.

Nagpal A, Needham K, Lane D, Ayton S, Redvers R, John M Cancers (Basel). 2023; 15(4).

PMID: 36831558 PMC: 9954089. DOI: 10.3390/cancers15041216.

Screening of Botanical Drugs against SARS-CoV-2 Entry Reveals Novel Therapeutic Agents to Treat COVID-19.

Cao J, Liu Y, Zhou M, Dong S, Hou Y, Jia X Viruses. 2022; 14(2).

PMID: 35215943 PMC: 8877376. DOI: 10.3390/v14020353.

Potent efficacy of MCL-1 inhibitor-based therapies in preclinical models of mantle cell lymphoma.

Dengler M, Teh C, Thijssen R, Gangoda L, Lan P, Herold M Oncogene. 2019; 39(9):2009-2023.

PMID: 31772331 DOI: 10.1038/s41388-019-1122-x.

A novel tankyrase inhibitor, MSC2504877, enhances the effects of clinical CDK4/6 inhibitors.

Menon M, Elliott R, Bowers L, Balan N, Rafiq R, Costa-Cabral S Sci Rep. 2019; 9(1):201.

PMID: 30655555 PMC: 6336890. DOI: 10.1038/s41598-018-36447-4.

References

White E, Parker W, Macy L, Shaddix S, McCaleb G, Secrist 3rd J . Comparison of the effect of Carbovir, AZT, and dideoxynucleoside triphosphates on the activity of human immunodeficiency virus reverse transcriptase and selected human polymerases. Biochem Biophys Res Commun. 1989; 161(2):393-8. DOI: 10.1016/0006-291x(89)92611-9. View

Berman E, Krown S, Fanucchi M, Chou J, Hirsch M, Clarkson B . Synergistic cytotoxic effect of azidothymidine and recombinant interferon alpha on normal human bone marrow progenitor cells. Blood. 1989; 74(4):1281-6. View

Hayashi S, Fine R, Chou T, Currens M, Broder S, Mitsuya H . In vitro inhibition of the infectivity and replication of human immunodeficiency virus type 1 by combination of antiretroviral 2',3'-dideoxynucleosides and virus-binding inhibitors. Antimicrob Agents Chemother. 1990; 34(1):82-8. PMC: 171524. DOI: 10.1128/AAC.34.1.82. View

Buhles Jr W, Mastre B, TINKER A, Strand V, Koretz S . Ganciclovir treatment of life- or sight-threatening cytomegalovirus infection: experience in 314 immunocompromised patients. Rev Infect Dis. 1988; 10 Suppl 3:S495-506. DOI: 10.1093/clinids/10.supplement_3.s495. View

Shipman Jr C, Smith S, Carlson R, DRACH J . Antiviral activity of arabinosyladenine and arabinosylhypoxanthine in herpes simplex virus-infected KB cells: selective inhibition of viral deoxyribonucleic acid synthesis in synchronized suspension cultures. Antimicrob Agents Chemother. 1976; 9(1):120-7. PMC: 429485. DOI: 10.1128/AAC.9.1.120. View

Shipman Jr C . Evaluation of 4-(2-hydroxyethyl)-1-piperazineëthanesulfonic acid (HEPES) as a tissue culture buffer. Proc Soc Exp Biol Med. 1969; 130(1):305-10. DOI: 10.3181/00379727-130-33543. View

LOEWE S . The problem of synergism and antagonism of combined drugs. Arzneimittelforschung. 1953; 3(6):285-90. View

Kueng W, Silber E, Eppenberger U . Quantification of cells cultured on 96-well plates. Anal Biochem. 1989; 182(1):16-9. DOI: 10.1016/0003-2697(89)90710-0. View

Barer M, Lyon H, Drasar B . Quantitation of dye binding by cell monolayers in a microtiter system. Histochem J. 1986; 18(2-3):122-8. DOI: 10.1007/BF01675366. View

10.

Cheng Y, Grill S, Dutschman G, Frank K, Chiou J, Bastow K . Effects of 9-(1,3-dihydroxy-2-propoxymethyl)guanine, a new antiherpesvirus compound, on synthesis of macromolecules in herpes simplex virus-infected cells. Antimicrob Agents Chemother. 1984; 26(3):283-8. PMC: 176152. DOI: 10.1128/AAC.26.3.283. View

11.

Schwartz P, Shipman Jr C, Carlson R, DRACH J . Thermal inactivation as a means of inhibiting the serum-associated deamination of 9-beta-D Arabinofuranosyladenine in tissue culture media. Antimicrob Agents Chemother. 1974; 5(3):337-43. PMC: 428970. DOI: 10.1128/AAC.5.3.337. View

12.

Hochster H, Dieterich D, Bozzette S, Reichman R, Connor J, Liebes L . Toxicity of combined ganciclovir and zidovudine for cytomegalovirus disease associated with AIDS. An AIDS Clinical Trials Group Study. Ann Intern Med. 1990; 113(2):111-7. DOI: 10.7326/0003-4819-113-2-111. View

13.

Prichard M, Shipman Jr C . A three-dimensional model to analyze drug-drug interactions. Antiviral Res. 1990; 14(4-5):181-205. DOI: 10.1016/0166-3542(90)90001-n. View

14.

Chou T, Talalay P . Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul. 1984; 22:27-55. DOI: 10.1016/0065-2571(84)90007-4. View

15.

St Clair M, Miller W, Miller R, Lambe C, Furman P . Inhibition of cellular alpha DNA polymerase and herpes simplex virus-induced DNA polymerases by the triphosphate of BW759U. Antimicrob Agents Chemother. 1984; 25(2):191-4. PMC: 185472. DOI: 10.1128/AAC.25.2.191. View

16.

Jacobson M, de Miranda P, Gordon S, Blum M, Volberding P, Mills J . Prolonged pancytopenia due to combined ganciclovir and zidovudine therapy. J Infect Dis. 1988; 158(2):489-90. DOI: 10.1093/infdis/158.2.489. View

17.

Yarchoan R, Klecker R, Weinhold K, Markham P, Lyerly H, Durack D . Administration of 3'-azido-3'-deoxythymidine, an inhibitor of HTLV-III/LAV replication, to patients with AIDS or AIDS-related complex. Lancet. 1986; 1(8481):575-80. DOI: 10.1016/s0140-6736(86)92808-4. View

18.

Richman D, Fischl M, GRIECO M, Gottlieb M, Volberding P, Laskin O . The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. N Engl J Med. 1987; 317(4):192-7. DOI: 10.1056/NEJM198707233170402. View

19.

Jacobson M, ODonnell J, Porteous D, BRODIE H, Feigal D, Mills J . Retinal and gastrointestinal disease due to cytomegalovirus in patients with the acquired immune deficiency syndrome: prevalence, natural history, and response to ganciclovir therapy. Q J Med. 1988; 67(254):473-86. View

20.

Fischl M, Richman D, GRIECO M, Gottlieb M, Volberding P, Laskin O . The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. N Engl J Med. 1987; 317(4):185-91. DOI: 10.1056/NEJM198707233170401. View