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[Covalently bound residues: theoretical aspects].

V Burgat-Sacaze1, A Rico

  • 1Laboratoire de Toxicologie Biochimique et Métabolique, Ecole Nationale Vétérinaire de Toulouse, France.

Annales De Recherches Veterinaires. Annals of Veterinary Research
|January 1, 1990
PubMed
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Covalently bound residues (CBRs) are drug metabolites that bind irreversibly to tissues. While potentially toxic to target species, CBRs exhibit low bioavailability and pose minimal risk to consumers.

Area of Science:

  • Pharmacokinetics
  • Toxicology
  • Biochemistry

Context:

  • Covalently bound residues (CBRs) are formed when drugs or their metabolites bind to macromolecules.
  • These residues are not extractable using standard laboratory techniques.
  • CBRs are detected as non-extractable radioactivity in tissues after administering radiolabeled drugs.

Purpose:

  • To discuss the characteristics of covalently bound residues.
  • To explain the formation and properties of CBRs.
  • To analyze the toxicological and pharmacokinetic implications of CBRs.

Summary:

  • Covalent binding involves reactive drug metabolites (electrophiles or free radicals) forming irreversible, non-specific bonds with endogenous molecules like proteins and lipids.
  • The released compound after bond cleavage is not the original reactive metabolite.

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  • CBRs represent the largest fraction of late residues and have low bioavailability.

    • Impact:

    • Covalently bound metabolites may exhibit toxicity in the target species.
    • However, CBRs likely pose low toxicity risks to consumers.
    • Understanding CBRs is crucial for drug safety assessment and residue analysis.