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Mitochondrial Injury

Lessons from the Fialuridine Trial

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Summary

Fialuridine is an antiviral agent with potent activity against hepatitis B virus replication in vitro and in vivo. In a phase II study, 7 of 15 patients experienced severe toxicity due to the drug after 9 to 13 weeks of treatment. Adverse effects included nausea, vomiting and painful paraesthesia; subsequently, hepatic failure, pancreatitis, neuropathy, myopathy and lactic acidosis developed, probably due to multisystem mitochondrial toxicity.

Possible mechanisms of fialuridine toxicity include mitochondrial injury and pyruvate oxidation inhibition. While other nucleoside analogues have shown evidence of inducing mitochondrial injury (zidovudine, didanosine, zalcitabine), others to date have not (lamivudine, famciclovir). Specific recommendations for future study of existing and new nucleoside analogues include testing for toxicity after prolonged incubation, specific investigations to measure mitochondrial function, toxicological tests and well designed clinical trials with appropriate testing to monitor for any adverse effects on mitochondrial integrity and function.

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Authors and Affiliations

  1. Department of Internal Medicine II (Section Hepatology), Erasmus University Hospital, Rotterdam, The Netherlands

    Pieter Honkoop, Robert A. de Man &  Solko W. Schalm

  2. Department of Biochemistry, Erasmus University Hospital, Rotterdam, The Netherlands

    Hans R. Scholte

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  1. Pieter Honkoop
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  2. Hans R. Scholte
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  3. Robert A. de Man
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  4. Solko W. Schalm
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Correspondence to Solko W. Schalm.

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Honkoop, P., Scholte, H.R., de Man, R.A. et al. Mitochondrial Injury. Drug-Safety 17, 1–7 (1997). https://doi.org/10.2165/00002018-199717010-00001

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