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Effects of tolcapone, a catechol-O-methyltransferase inhibitor, on motor symptoms and pharmacokinetics of levodopa in patients with Parkinson's disease

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Summary

The effects of tolcapone, a catechol-O-methyltransferase inhibitor, on the bioavailability and efficacy of levodopa were evaluated in 12 patients with Parkinson's disease (PD), 8 of whom showed signs of daily motor fluctuations (wearing-off phenomenon). Motor disabilities were assessed in 12 patients at 7 time points before and after the chronic administration of tolcapone using the Unified Parkinson's Disease Rating Scale (UPDRS). The UPDRS score was improved at all points of determination. Eight patients with wearing-off phenomenon on levodopa showed symptomatic improvement on the combination. The area under the curve (AUC) for levodopa increased by 34% (p=0.0059) after the administration of tolcapone. The elimination half-life (T1/2) of levodopa was significantly prolonged by 81% (p=0.0001) after the treatment. The AUC of 3-O-methyldopa, a metabolite of levodopa, was decreased by 79% (p=0.0001) and the Cmax (maximum concentration) was also decreased by 80% after the administration (p=0.0001) of tolcapone. The combination of tolcapone and levodopa was well tolerated. Our findings suggest that tolcapone improves the pharmacokinetics of levodopa in plasma and motor symptoms of fluctuating PD patients. It is suggested that tolcapone may be a useful drug adjunct to levodopa in treating patients with PD with wearing-off phenomena.

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Author notes

  1. M. Yamamoto

    Present address: Department of Neurology, Kagawa Prefectural Central Hospital, Japan

Authors and Affiliations

  1. Department of Neurology, Tokyo Metropolitan Ebara Hospital, Japan

    M. Yokochi

  2. Department of Neurology, National Utano Hospital, Japan

    S. Kuno

  3. Department of Neurology, Juntendo University, Japan

    Y. Hattori & Y. Mizuno

  4. Department of Pharmacokinetics and Metabolism, Nippon Roche Research Center, Japan

    Y. Tsukamoto

  5. Neurological Clinic, Iwate Medical University, Japan

    H. Narabayashi

  6. Department of Neurology, Iwate Medical University, Japan

    H. Tohgi

  7. Department of Neurology, Kitasato University, Japan

    H. Kowa

  8. Department of Internal Medicine, Shinsyu University, Japan

    N. Yanagisawa

  9. Department of Neurology, Institute of Brain Research, Faculty of Medicine, University of Tokyo, Japan

    I. Kanazawa

Authors
  1. M. Yamamoto
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  2. M. Yokochi
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  3. S. Kuno
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  4. Y. Hattori
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  6. H. Narabayashi
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  7. H. Tohgi
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  8. Y. Mizuno
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  9. H. Kowa
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  10. N. Yanagisawa
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  11. I. Kanazawa
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Yamamoto, M., Yokochi, M., Kuno, S. et al. Effects of tolcapone, a catechol-O-methyltransferase inhibitor, on motor symptoms and pharmacokinetics of levodopa in patients with Parkinson's disease. J. Neural Transmission 104, 229–236 (1997). https://doi.org/10.1007/BF01273183

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  • DOI: https://doi.org/10.1007/BF01273183

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