• 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.

  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},
  volume={24 11},
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.

The present study demonstrates the utility of an in vitro-in vivo correlative approach in the selection of an optimum prodrug candidate of L-767,679, a potent fibrinogen receptor antagonist, and considered the ethyl ester as a promising candidate for clinical evaluation as a fibrine receptor antagonist prodrug.

In vitro and in vivo evaluations of intestinal barriers for the zwitterion L-767,679 and its carboxyl ester prodrug L-775,318. Roles of efflux and metabolism.

Results suggested that the intestinal absorption of I was limited not by intestinal efflux or metabolism but more likely by the low lipophilicity of I, however, an efflux system played an important role in limiting the absorption of II.


In vitro metabolism using liver S9 fractions from both cynomolgus monkeys and humans and oral bioavailability in cynomolia monkeys was investigated to select the prodrug most likely to exhibit optimal pharmacokinetic profiles in humans, and MGS0210 seems to be a promising candidate among MGS0039 pro drugs.

Nonclinical pharmacokinetics of BMS‐292655, a water‐soluble prodrug of the antifungal ravuconazole

The similarity in the hydrolysis of BMS‐292655 when incubated with human and monkey S9 in vitro, coupled with the effective release of B MS‐207147 from BMS•2926 55 upon i.v. administration to monkeys, is consistent with this conclusion.

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.