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Mechanism of Intestinal Absorption of Ranitidine and Ondansetron: Transport Across Caco-2 Cell Monolayers

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Abstract

We have investigated the transport of ranitidine and ondansetron across the Caco-2 cell monolayers. The apparent permeability coefficients (P app) were unchanged throughout the concentration range studied, indicating a passive diffusion pathway across intestinal mucosa. No metabolism was observed for ranitidine and ondansetron during the incubation with Caco-2 cell monolayers. P app values for ranitidine and ondansetron (bioavailability of 50 and ∼100% in humans, respectively) were 1.03 ± 0.17 × 10−7 and 1.83 ± 0.055 × 10−5 cm/sec, respectively. The P app value for ranitidine was increased by 15- to 20-fold in a calcium-free medium or in the transport medium containing EDTA, whereas no significant change occurred with ondansetron, indicating that paracellular passive diffusion is not rate determining for ondansetron. Uptake of ondansetron by Caco-2 cell monolayers was 20- and 5-fold higher than that of ranitidine when the uptake study was carried out under sink conditions and at steady state. These results suggest that ranitidine and ondansetron are transported across Caco-2 cell monolayers predominantly via paracellular and transcellular pathways, respectively.

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Authors and Affiliations

  1. Department of Drug Metabolism, Glaxo Inc. Research Institute, Research Triangle Park, North Carolina, 27709

    Liang-Shang Gan & Dhiren Thakker

  2. Department of Clinical Pharmacology, Glaxo Inc. Research Institute, Research Triangle Park, North Carolina, 27709

    Poe-Hirr Hsyu & J. Frederick Pritchard

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  1. Liang-Shang Gan
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  2. Poe-Hirr Hsyu
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  3. J. Frederick Pritchard
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  4. Dhiren Thakker
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Gan, LS., Hsyu, PH., Pritchard, J.F. et al. Mechanism of Intestinal Absorption of Ranitidine and Ondansetron: Transport Across Caco-2 Cell Monolayers. Pharm Res 10, 1722–1725 (1993). https://doi.org/10.1023/A:1018965929419

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