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Pharmacokinetics of Levodopa, Carbidopa, and 3-O-Methyldopa Following 16-hour Jejunal Infusion of Levodopa-Carbidopa Intestinal Gel in Advanced Parkinson’s Disease Patients

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Abstract

Motor complications of Parkinson’s disease (PD) are a consequence of pulsatile dopaminergic stimulation from standard oral levodopa therapy. Levodopa–carbidopa intestinal gel (LCIG) is infused continuously via an intrajejunal percutaneous gastrostomy tube. This was the first study designed to characterize the full pharmacokinetic profiles of levodopa, carbidopa, and levodopa metabolite, 3-O-methyldopa (3-OMD) with 16-h LCIG infusion. Nineteen advanced PD patients (mean age, 65 years) who were on LCIG therapy for ≥30 days were enrolled. Patients received their individualized LCIG infusion doses, and serial pharmacokinetic samples were collected. Eighteen patients completed the study; 19 were assessed for safety. Mean (SD) total levodopa and carbidopa doses were 1,580 (403) and 395 (101) mg, respectively. Mean (SD) C avg (μg/mL) were 2.9 (0.84) for levodopa, 17.1 (4.99) for 3-OMD, and 0.22 (0.08) for carbidopa. The degree of fluctuation [defined as (C max − C min)/C avg] in levodopa, 3-OMD, and carbidopa plasma concentrations was very low (0.52, 0.21, and 0.96, respectively) during hours 2–16 of infusion. Accordingly, the within-subject coefficients of variation in levodopa, 3-OMD, and carbidopa concentrations were low (13%, 6%, and 19%, respectively). Three patients (16%) reported ≥1 treatment-emergent adverse event; none were considered severe. Continuous intrajejunal LCIG infusion maintained stable plasma levodopa levels over 16 h. Consistent exposure has been shown to reduce motor and nonmotor complications associated with oral medications. LCIG was well tolerated, consistent with previous reports.

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Acknowledgments

This study was sponsored by Abbott. The study was conducted and clinical laboratory tests were performed by Quintiles. The authors thank Dr. Holger Honig and Research Nurses Anne Rüssmann and Sandra Leimbach of the Neurology clinic at Klinikum-Bremerhaven, and the staff of the Neurology clinic at Uppsala University Hospital for their assistance in the completion of the study. Nathan R. Rustay and Michelle M. Tangredi, of Abbott, provided medical writing support in the development of the manuscript.

Financial Disclosure/Conflict of Interest Concerning the Research Related to the Manuscript

Dr. Nyholm has been a study investigator in Abbott-sponsored studies and has received compensation from Abbott for serving as a consultant. Prof. Odin has been a study investigator in Abbott-sponsored studies and has received compensation from Abbott for serving as a consultant and lecturer. Dr. Johansson has been a study investigator in Abbott-sponsored studies and has received compensation from Abbott for serving as a lecturer. Drs Chatamra, Locke, Dutta, and Othman are employees of Abbott and receive compensation including salary, stock, and/or stock options from Abbott.

Funding source

Abbott funded this study and provided the study drug.

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Authors and Affiliations

  1. Department of Neuroscience, Neurology, Uppsala University, Uppsala, Sweden

    Dag Nyholm & Anders Johansson

  2. Department of Neurology, Skane University Hospital, Lund, Sweden

    Per Odin

  3. Department of Neurology, Klinikum-Bremerhaven, Bremerhaven, Germany

    Per Odin

  4. Department of Clinical Neuroscience, Neurology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

    Anders Johansson

  5. Neuroscience Development, Abbott Laboratories, Abbott Park, Illinois, USA

    Krai Chatamra

  6. Clinical Pharmacology and Pharmacometrics, Abbott Laboratories, 100 Abbott Park Rd, Bldg AP13A-3, Abbott Park, Illinois, 60064, USA

    Charles Locke, Sandeep Dutta & Ahmed A. Othman

  7. Department of Pharmaceutics, Faculty of Pharmacy, Cairo University, Cairo, Egypt

    Ahmed A. Othman

Authors
  1. Dag Nyholm
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  2. Per Odin
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  4. Krai Chatamra
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  7. Ahmed A. Othman
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Corresponding author

Correspondence to Ahmed A. Othman.

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Nyholm, D., Odin, P., Johansson, A. et al. Pharmacokinetics of Levodopa, Carbidopa, and 3-O-Methyldopa Following 16-hour Jejunal Infusion of Levodopa-Carbidopa Intestinal Gel in Advanced Parkinson’s Disease Patients. AAPS J 15, 316–323 (2013). https://doi.org/10.1208/s12248-012-9439-1

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  • DOI: https://doi.org/10.1208/s12248-012-9439-1

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