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Calculation of the gastric absorption rate constants of 5-substituted barbiturates through theR m values or substituent ΔR m constants in reversed-phase partition chromatography

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Abstract

A linear correlation between the logarithm of the in situgastric absorption rate constants (ka)of 5-substituted barbiturates and their Rm values in selected reversed-phase partition chromatographic systems is demonstrated, as well as between the Δlog ka and the ΔRm derived parameters. On the basis of the chromatographic behavior of 14 closely related compounds of this series, the substituent ΔRm constants for the main functional groups are calculated, so that the gastric absorption constants of nontested barbiturates can be predicted with close approximation. Predicted Rm and log ka values show an excellent correlation with log 1/C values taken from pharmacological literature data. The migration mechanisms involved in reversed-phase partition chromatography are discussed in connection with the results obtained with other types of partition systems and with bulk-phase solvents. The possible relationships between chromatographic parameters and absorption rate constants found from absorption sites other than the stomach are outlined; as well as the advantages and limitations of the procedure.

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Authors and Affiliations

  1. Practical Pharmacy Department, Section of Biopharmaceutics, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain

    José M. Plá-Delfina, Joaquín Moreno, Juan Durán & Alfonso del Pozo

Authors
  1. José M. Plá-Delfina
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  2. Joaquín Moreno
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  3. Juan Durán
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  4. Alfonso del Pozo
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Plá-Delfina, J.M., Moreno, J., Durán, J. et al. Calculation of the gastric absorption rate constants of 5-substituted barbiturates through theR m values or substituent ΔR m constants in reversed-phase partition chromatography. Journal of Pharmacokinetics and Biopharmaceutics 3, 115–141 (1975). https://doi.org/10.1007/BF01066019

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  • DOI: https://doi.org/10.1007/BF01066019

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