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Role of Ademetionine (S-Adenosylmethionine) in Cyclosporin-Induced Cholestasis

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Abstract

Objective: To determine the efficacy of ademetionine (S-adenosylmethionine, SAME) administration in preventing hepatotoxicity in patients undergoing long-term cyclosporin treatment.

Design: Randomised, controlled, double-blind trial followed up for 3 months.

Setting: Subjects were studied for a period of 10 days in hospital and then followed up in the outpatient unit for 3 months.

Patients: 72 male patients with psoriasis, of whom 36 were treated with cyclosporin and 36 with cyclosporin plus ademetionine.

Interventions: Cyclosporin treatment alone (10 mg/kg/day) was compared with treatment with the same dosage of cyclosporin in combination with ademetionine 400 mg/day.

Main outcome measures: Serum fractioned bilirubin, γ-glutamyltransferase, alkaline phosphatase and transaminases, plasma malondialdehyde and 4-hydroxynonenal, and erythrocyte glutathione peroxidase were determined.

Results: Hepatotoxicity and cholestasis were observed in 15 of 36 patients treated with cyclosporin alone, whereas no cases of liver cytotoxicity were observed in the group treated with cyclosporin in combination with ademetionine (p < 0.005). Moreover, the study results revealed a significant difference in oxidation-reduction balance between the two groups, with more marked oxidative stress in patients on cyclosporin alone.

Conclusions: Ademetionine may protect the liver against potentially hepatotoxic substances, such as cyclosporin, and coadministration of ademetionine should therefore be considered when hepatotoxic drugs are used.

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Acknowledgements

This manuscript was supported by a grant from the Italian University Ministry (MURST). The authors thank Ms Moira Mcpherson for her assistance in translation.

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Authors and Affiliations

  1. Department of Internal and Emergency Medicine, University of Catania, Catania, Italy

    Sergio Neri, D. Ierna, B. Mauceri, G. Abate, F. Bordonaro & D. Cilio

  2. Department of Internal Medicine, Angiology Unit, University of Catania, Catania, Italy

    S. S. Signorelli

  3. Department of Geriatrics, University of Catania, Catania, Italy

    M. Malaguarnera

Authors
  1. Sergio Neri
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  2. S. S. Signorelli
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  3. D. Ierna
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  4. B. Mauceri
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  5. G. Abate
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  6. F. Bordonaro
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  7. D. Cilio
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  8. M. Malaguarnera
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Neri, S., Signorelli, S.S., Ierna, D. et al. Role of Ademetionine (S-Adenosylmethionine) in Cyclosporin-Induced Cholestasis. Clin. Drug Investig. 22, 191–195 (2002). https://doi.org/10.2165/00044011-200222030-00006

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  • DOI: https://doi.org/10.2165/00044011-200222030-00006

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