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The effect of food on the high clearance drug asenapine after sublingual administration to healthy male volunteers

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

Abstract

Purpose

To determine the effects of food on the pharmacokinetics of sublingual asenapine.

Methods

Healthy male volunteers (n = 26, age 19–53 years) randomly received a single sublingual dose of asenapine 5 mg after ≥10 h fasting (Treatment A, reference), after a high-fat meal (Treatment B) and after ≥10 h fasting with a high-fat meal at 4 h post-dose (Treatment C). Blood samples were drawn over 72 h to measure asenapine plasma concentrations. Effects of food intake on asenapine pharmacokinetics were assessed using bioequivalence criteria and evaluated using a compartmental modelling analysis.

Results

Compared with the reference, mean asenapine exposure (AUC0-last and AUC0-∞) was approximately 20 % lower after intake of a high-fat meal prior to dosing, whereas Cmax decreased by only about 10 %. When a high-fat meal was taken 4 h post-dose in the fasting state, asenapine concentrations were similar to the reference during the first 4 h post-dose. After the meal intake, asenapine concentrations decreased quickly for several hours. Compartmental modelling indicated that a transient 2.5-fold increase in asenapine clearance after eating could explain the asenapine concentration–time profiles for both food regimens.

Conclusions

To our knowledge, this is the first study investigating the effect of food upon the sublingual administration of a drug. A high-fat meal taken before or 4 h post-dose of sublingual asenapine indirectly caused a transient increase in liver blood flow that resulted in a temporal increase in asenapine clearance. As the effects on asenapine exposure were small and not clinically relevant, no additional restrictions are required for the timing of food intake in relation to asenapine dosing.

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Acknowledgements

This study was conducted by C&T Paradigm, Antwerp, Belgium in 2005 under the responsibility of Luc Tritsmans, MD. Medical writing and editorial assistance was provided by Bagi Ravishankar, PhD, of PPSI, New Jersey (a PAREXEL company) and was funded by Merck & Co. Inc., Whitehouse Station, New Jersey, USA.

Funding/Conflict of Interest Statement

This study was funded by Merck & Co. Inc., Whitehouse Station, New Jersey, USA, and all authors were employees of Merck & Co at the time the study was conducted.

Author information

Author notes

  1. Pierre A. M. Peeters

    Present address: Centre for Human Drug Research, Leiden, The Netherlands

Authors and Affiliations

  1. Early Stage Development, Merck Sharp & Dohme, PO Box 20, 5340 BH, Oss, The Netherlands

    Peter Dogterom & Pierre A. M. Peeters

  2. Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Sharp & Dohme, Oss, The Netherlands

    Rik de Greef

Authors
  1. Peter Dogterom
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Correspondence to Peter Dogterom.

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Dogterom, P., de Greef, R. & Peeters, P.A.M. The effect of food on the high clearance drug asenapine after sublingual administration to healthy male volunteers. Eur J Clin Pharmacol 71, 65–74 (2015). https://doi.org/10.1007/s00228-013-1587-4

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  • DOI: https://doi.org/10.1007/s00228-013-1587-4

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