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The effect of different dosing regimens of levodopa/carbidopa/entacapone on plasma levodopa concentrations

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Background

Repeated dosing of levodopa/carbidopa/entacapone (LCE) has shown a favourable pharmacokinetic (PK) profile compared with levodopa/carbidopa (LC), but increases maximum plasma levodopa concentrations (Cmax) during the day. High levodopa concentrations are associated with peak-dose dyskinesias.

Purpose

To determine whether administering LCE 75/18.5/200 and 125/31.5/200 mg (LCE 75 and LCE 125) following a morning dose of LCE 100/25/200 and 150/37.5/200 mg (LCE 100 and LCE 150), respectively, would avoid the increase in levodopa Cmax values observed during multiple dosing of LCE 100 and LCE 150.

Methods

This was an open, randomized, three-period, crossover PK trial in healthy volunteers (n = 19). Subjects were randomized to Group 1 or 2. Group 1 received in random sequence: LCE 150 followed by LCE 125 three times daily (tid); LCE 150 four times daily (qid); LC 150 qid. Group 2 received in random sequence: LCE 100 followed by LCE 75 tid; LCE 100 qid; LC 100 qid. Levodopa Cmax, minimum plasma concentration (Cmin), area under the curve (AUC0−14) and peak–trough fluctuation (PTF) were calculated up to 14 h after the first dose.

Results

Levodopa Cmax was not increased when the LCE dose was decreased by 25 mg after the morning dose. In comparison to LC, levodopa Cmin levels and AUC0−14 values for LCE were significantly higher, while the levodopa PTF was significantly smaller.

Conclusions

Reducing the dose of LCE by 25 mg following the first morning dose results in a more consistent levodopa Cmax profile, avoiding levodopa accumulation while maintaining significantly higher Cmin levels and AUC0−14 values compared with LC.

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Acknowledgements

The authors would like to thank Nadia Hashash, PhD, for editorial support in preparation of the manuscript. Editorial support was funded by Orion Corporation, Orion Pharma and Novartis Pharmaceuticals AG.

Conflicts of interest

All authors are employees of Orion Pharma.

Author information

Authors and Affiliations

  1. Phase I Unit, Orion Pharma, Orion Corporation, Espoo, Finland

    Kimmo Ingman

  2. Orion Pharma, Orion Corporation, Turku, Finland

    Tarja Naukkarinen, Irja Korpela, Mikko Kuoppamäki & Juha Ellmén

  3. Orion Pharma, Orion Corporation, Kuopio, Finland

    Mikko Vahteristo

  4. Department of Neurology, University of Turku, Turku, Finland

    Mikko Kuoppamäki

  5. Orionintie 1, P.O. Box 65, 02101, Espoo, Finland

    Kimmo Ingman

Authors
  1. Kimmo Ingman
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  2. Tarja Naukkarinen
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  3. Mikko Vahteristo
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  4. Irja Korpela
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  5. Mikko Kuoppamäki
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  6. Juha Ellmén
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Corresponding author

Correspondence to Kimmo Ingman.

Additional information

EudraCT number: 2009-015625-37

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Ingman, K., Naukkarinen, T., Vahteristo, M. et al. The effect of different dosing regimens of levodopa/carbidopa/entacapone on plasma levodopa concentrations. Eur J Clin Pharmacol 68, 281–289 (2012). https://doi.org/10.1007/s00228-011-1121-5

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  • DOI: https://doi.org/10.1007/s00228-011-1121-5

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