• Corpus ID: 10226197

Species and organ differences in first-pass metabolism of the ester prodrug L-751,164 in dogs and monkeys. In vivo and in vitro studies.

@article{Prueksaritanont1996SpeciesAO,
  title={Species and organ differences in first-pass metabolism of the ester prodrug L-751,164 in dogs and monkeys. In vivo and in vitro studies.},
  author={Thomayant Prueksaritanont and L M Gorham and Joan D. Ellis and Carmen L. Fern{\'a}ndez-Metzler and P Deluna and J R Gehret and Katie L. Strong and Jerome H. Hochman and Ben C. Askew and Mark E. Duggan and John D. Gilbert and J. H. Lin and Kamlesh P. Vyas},
  journal={Drug metabolism and disposition: the biological fate of chemicals},
  year={1996},
  volume={24 11},
  pages={
          1263-71
        }
}
The pharmacokinetics and bioavailability of L-751,164, an ethyl ester prodrug of a potent fibrinogen receptor antagonist, L-742,998, were studied in beagle dogs and rhesus monkeys. In both species, L-751,164 exhibited high clearance. After an intravenous dose, L-751,164 was converted to the parent L-742,998 to the extent of approximately 20% in dogs and 90% in monkeys. After oral administration of the prodrug, however, the bioavailability, measured either as the prodrug or as the active parent… 

In vitro and in vivo evaluations of the metabolism, pharmacokinetics, and bioavailability of ester prodrugs of L-767,679, a potent fibrinogen receptor antagonist: an approach for the selection of a prodrug candidate.

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Extrahepatic Drug-Metabolizing Enzymes and Their Significance

Extrahepatic DMEs are also involved in bioactivation of prodrugs and formation of reactive metabolites that may interact with cellular components, resulting in organ-specific toxicity.

A Comparison of the Bioconversion Rates and the Caco-2 Cell Permeation Characteristics of Coumarin-Based Cyclic Prodrugs and Methylester-Based Linear Prodrugs of RGD Peptidomimetics

The coumarin-based cyclic prodrugs 3a and 3b were chemically less stable, but metabolically more stable, than the methylester-based linear prodrug's, which were chemically more stable to chemical hydrolysis and more stable in biological media containing esterase activity.