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Levetiracetam Pharmacokinetics in Japanese Subjects with Renal Impairment

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Abstract

Background and Objective

The anti-epileptic drug levetiracetam is excreted renally. The objective of this trial was to evaluate the pharmacokinetics of levetiracetam in Japanese patients with renal impairment including end-stage renal disease (ESRD) to confirm that existing dosing instructions—based on data from European patients—are appropriate in a Japanese population.

Methods

This was a nonrandomised, open-label trial. Six participants were allocated to each of five groups (normal renal function, mild, moderate and severe renal impairment and ESRD); 30 participants in total. Participants received a single dose of levetiracetam 500 mg (normal or mild), 250 mg (moderate or severe), or 500 mg followed by 250 mg post-haemodialysis (ESRD). Blood and urine samples were obtained serially for levetiracetam and metabolite determinations. Noncompartmental pharmacokinetic parameters were calculated and steady-state profiles were simulated using the superposition method.

Results

In this trial, levetiracetam total clearance decreased proportionally with creatinine clearance: 52, 31, 25, 20 and 11 mL/min/1.73 m2 in healthy controls and in patients with mild, moderate, severe renal impairment, and ESRD, respectively. Simulated levetiracetam plasma profiles using the recommended dose adjustments were within the range for normal renal function. Overall, results from this trial were consistent with historical European data.

Conclusion

These findings confirm that the dosing instructions are appropriate for Japanese patients with renal impairment including ESRD.

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Acknowledgments

UCB Pharma sponsored this study and was involved in the design and conduct of the study, and collection, management, and analysis of the data. Nathalie Toublanc, Armel Stockis and Junichi Yamamoto are employees of UCB Pharma. Yuji Kumagai was the medical advisor and is a Professor of the Kitasato Clinical Research Center, Kitasato University, Japan. The authors thank Katsumi Yoshida, RPh for statistical assistance, Ludovicus Staelens (both UCB Pharma) who was responsible for the bioanalysis, and the principal investigators Teruo Fukumoto, MD, Tadayuki Hiroki, MD (both from Kurume Clinical Pharmacology Clinic), and Tokuro Kobayashi, MD (Moriya Keiyu Hospital). Fiona Swain of Mediwrite Ltd, United Kingdom provided medical writing support funded by UCB Pharma, and Azita Tofighy, UCB Pharma, provided editorial support and coordinated the manuscript development process.

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Authors and Affiliations

  1. UCB Pharma, Shinjuku Grand Tower, 8-17-1 Nishi-Shinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan

    Junichi Yamamoto

  2. UCB Pharma, Chemin du Foriest, 1420, Braine-l’Alleud, Belgium

    Nathalie Toublanc & Armel Stockis

  3. Kitasato University, Kanagawa, Japan

    Yuji Kumagai

Authors
  1. Junichi Yamamoto
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  2. Nathalie Toublanc
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  3. Yuji Kumagai
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  4. Armel Stockis
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Corresponding authors

Correspondence to Junichi Yamamoto or Nathalie Toublanc.

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Yamamoto, J., Toublanc, N., Kumagai, Y. et al. Levetiracetam Pharmacokinetics in Japanese Subjects with Renal Impairment. Clin Drug Investig 34, 819–828 (2014). https://doi.org/10.1007/s40261-014-0237-7

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  • DOI: https://doi.org/10.1007/s40261-014-0237-7

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