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Differences in lercanidipine systemic exposure when administered according to labelling: in fasting state and 15 minutes before food intake

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

Abstract

Purpose

The aim of this study was to compare the systemic exposure of lercanidipine (Zanidip) after oral administration in the fasted state and 15 min before food intake (meals) to investigate if the recommendations in the Summary of Product Characteristics (SPC) with respect to the intake of meals are adequate.

Methods

The results of three pilot bioequivalence studies performed to develop a lercanidipine generic product, where Zanidip was administered consistently as reference product in the fasted state or 15 min before a standard breakfast, were compared to estimate the drug–food interaction and the similarity of the methods of administration defined in the SPC.

Results

The ingestion of a standard (non-high-fat, non-high-calorie) meal 15 min after drug intake increased the area under the concentration–time curve (AUC0-t) of S-lercanidipine by 1.78-fold [90% confidence interval (CI) 1.48–2.15, P < 0.0001] and the maximum concentration (Cmax) of S-lercanidipine by 1.82-fold (90% CI 1.46–2.28, P < 0.0001). These values are close to the twofold increase that has been described when Zanidip was taken immediately after a carbohydrate-rich meal. Higher levels would be expected with a high-fat, high-calorie meal.

Conclusions

As intake with a carbohydrate-rich meal is not recommended in the SPC of Zanidip because a twofold difference was considered to be clinically relevant, the intake of lercanidipine only 15 min before food intake does not seem to be consistent with this recommendation. The Marketing Authorisation Holder should clarify the dosing instructions in relation to meals and identify a sufficient time-lapse to ensure an exposure similar to that obtained in phase III clinical efficacy studies.

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Acknowledgements

We thank the Complutense University and Madrid Community Administration and its research group number 910939.

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Authors and Affiliations

  1. Departamento Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040, Madrid, Spain

    Covadonga Álvarez

  2. Laboratorios Normon S.A., Ronda Valdecarrizo 6, 28760, Tres Cantos, Madrid, Spain

    Estrella Gómez, Marta Simón & Carlos Govantes

  3. Clinical Pharmacology Service, Hospital Universitario la Paz, School of Medicine, Universidad Autónoma de Madrid, Arzobispo Morcillo s/n, 28029, Madrid, Spain

    Pedro Guerra & Jesús Frías

  4. Division of Pharmacology and Clinical Evaluation, General Subdirectorate for Human Use Medicines, Spanish Agency for Medicines and Health Care Products, C/ Campezo 1, Edificio 8, Planta 2 A, 28022, Madrid, Spain

    Alfredo García-Arieta

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  1. Covadonga Álvarez
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  2. Estrella Gómez
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  3. Marta Simón
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  4. Carlos Govantes
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  5. Pedro Guerra
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  6. Jesús Frías
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  7. Alfredo García-Arieta
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Corresponding author

Correspondence to Alfredo García-Arieta.

Additional information

This manuscript presents the personal opinion of the author Alfredo García-Arieta and does not necessarily represent the views or policy of the Spanish Agency for Medicines and Health Care Products.

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Álvarez, C., Gómez, E., Simón, M. et al. Differences in lercanidipine systemic exposure when administered according to labelling: in fasting state and 15 minutes before food intake. Eur J Clin Pharmacol 68, 1043–1047 (2012). https://doi.org/10.1007/s00228-012-1215-8

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  • DOI: https://doi.org/10.1007/s00228-012-1215-8

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