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Understanding the Oral Mucosal Absorption and Resulting Clinical Pharmacokinetics of Asenapine

AAPS PharmSciTech volume 13, pages 1110–1115 (2012)Cite this article

Abstract

Absorption of drugs from the oral cavity into the mucosal tissues is typically a fast event. Dissolved drugs partition into the mucosal membranes and within minutes will reach equilibrium with drug in solution in the oral cavity. However, this does not always equate to rapid drug appearance in the systemic circulation. This has been attributed to slow partitioning out of the mucosal tissues and into the systemic circulation. Based on information from literature, physicochemical properties of asenapine, and clinical data, we conclude that for sublingually administered asenapine, the exposure is primarily a function of rapid partitioning into the mucosal membranes. This is followed by slow partitioning out of the mucosal tissues and into the systemic circulation, leading to a T max value of about 1 h. The bioavailability of asenapine at doses below the saturation solubility in the mouth does not change and is controlled primarily by mass transport equilibrium. At doses above the saturation solubility, the bioavailability becomes more dependent not only on the distribution equilibrium but also on contact time in the mouth because additional variables (e.g. dissolution rate of the drug) need to be accounted for. These explanations are consistent with oral cavity absorption models from the literature and can be used to accurately describe the clinical data for asenapine.

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ACKNOWLEDGMENTS

The input and support from many colleagues within Pfizer and legacy Organon is highly appreciated by JB and KM.

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Authors and Affiliations

  1. Pharmaceutical Development, Worldwide Pharmaceutical Sciences, Pfizer Global Research and Development, Groton, Connecticut, 06340, USA

    Jeremy A. Bartlett

  2. Competence Center Process Technology, Purac Biochem, Gorinchem, The Netherlands

    Kees van der Voort Maarschalk

  3. Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands

    Kees van der Voort Maarschalk

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  1. Jeremy A. Bartlett
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Correspondence to Kees van der Voort Maarschalk.

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Bartlett, J.A., van der Voort Maarschalk, K. Understanding the Oral Mucosal Absorption and Resulting Clinical Pharmacokinetics of Asenapine. AAPS PharmSciTech 13, 1110–1115 (2012). https://doi.org/10.1208/s12249-012-9839-7

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  • DOI: https://doi.org/10.1208/s12249-012-9839-7

KEY WORDS

  • asenapine
  • exposure
  • oral mucosal absorption
  • T max