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Physico-chemical aspects of metabolically induced changes at the basic centre of two anti-emetics; relationship with in vivo membrane penetration

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Abstract

Partition coefficients in three solvent systems (1-octanol/ 0.1N NaOH,n-heptane/0.1N NaOH and toluene/0.1N NaOH), ionisation constants and thin-layer and reverse phase high pressure liquid chromatography retention data were determined for metoclopramide, its mono- and di-N-dealkylated metabolites, and for clebopride and its N-debenzylated metabolic product. Values for the additive-constitutive parameters π, ΔR m andx were calculated for the alkyl substituents at the basic centre of the two drugs, and the results are discussed.

The relationship between these physico-chemical parameters and thein vivo membrane penetrating capacity (this capacity was determined using buccal absorption measurements) is discussed.

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Author notes

  1. G. Huizing

    Present address: Central Hospital Pharmacy for The Hague, P.O. Box 43100, 2504, AC The Hague, The Netherlands

Authors and Affiliations

  1. Department of Pharmacy, Chelsea College, University of London, Manresa Road, SW3 6LX, London, UK

    G. Huizing & A. H. Beckett

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  1. G. Huizing
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  2. A. H. Beckett
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In honour of ProfessorPolderman on the occasion of his retirement.

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Huizing, G., Beckett, A.H. Physico-chemical aspects of metabolically induced changes at the basic centre of two anti-emetics; relationship with in vivo membrane penetration. Pharmaceutisch Weekblad Scientific Edition 2, 253–261 (1980). https://doi.org/10.1007/BF02272989

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  • DOI: https://doi.org/10.1007/BF02272989

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