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The impact of gastric pH, volume, and emptying on the food effect of ziprasidone oral absorption

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ABSTRACT

In a recent food effect clinical study, the authors concluded that a meal consisting of ≥500 kcal, regardless of fat content, produced the maximal bioavailability for ziprasidone. Using GastroPlus™, a commercially available pharmacokinetic simulation software, a semiphysiological model—a kind of physiologically based pharmacokinetic (PBPK) absorption model—was developed that could predict the concentration-time profiles when ziprasidone was administered with any one of the five test meals or fasting. Ziprasidone intravenous pharmacokinetics and oral absorption permeability were determined from clinical studies following the intravenous and duodenal infusion of ziprasidone to volunteers. From the detailed dietary information of each meal provided in the previously published food effect study, the stomach pH, volume, and gastric emptying could be predicted. Incorporating these meal-specific parameters into the model improved the predictions beyond the default fed/fasted parameters commonly used in the software. Compared to the default models, the improved models resulted in an improved prediction of the average ziprasidone concentration-time profile for each meal. Using this type of semiphysiological absorption model, we have shown that the dietary contents of the meals should be taken into account to predict food effects for ziprasidone and perhaps other BCS class I or II compounds.

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Notes

  1. pKa was determined by SCS at UNE College of Pharmacy.

  2. The ASF models are the best fits of experimental data across a diverse set of compounds (GastroPlus™ Manual, August 2013, Version 8.5, p. 168). The data could also be fitted to the Optimized logD Model by adjusting percent volume in the small and large intestines.

  3. The ASF model used in reference [16] was “Opt logD”, whereas in this work, the model used as “Opt logD Model SA/V 6.1”.

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Authors and Affiliations

  1. College of Pharmacy, University of New England, Portland, Maine, 04103, USA

    Steven C Sutton

  2. Celgene Corp, Summit, New Jersey, 07901, USA

    Richard Nause

  3. Pfizer, Inc., New York, New York, USA

    Kuan Gandelman

Authors
  1. Steven C Sutton
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  2. Richard Nause
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  3. Kuan Gandelman
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Correspondence to Steven C Sutton.

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Sutton, S.C., Nause, R. & Gandelman, K. The impact of gastric pH, volume, and emptying on the food effect of ziprasidone oral absorption. AAPS J 19, 1084–1090 (2017). https://doi.org/10.1208/s12248-017-0065-9

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  • DOI: https://doi.org/10.1208/s12248-017-0065-9

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