Burgat-Sacaze V, Rico A
Laboratoire de Toxicologie Biochimique et Métabolique, Ecole Nationale Vétérinaire de Toulouse, France.
Ann Rech Vet. 1990;21 Suppl 1:121S-127S.
Covalently bound residues (CBRs) result from the covalent binding of the parent drug or its metabolites to endogenous macromolecules. They are not extractable from the tissues by exhaustive extraction, denaturation and solubilization techniques, and are not the result of endogenous incorporation. They can be detected in the non-extractable radioactivity which persists in tissues after administration of radiolabeled drugs. The characteristics of CBRs are discussed. Covalent binding is an association of a reactive metabolite (electrophile or free radicals) and endogenous molecules (proteins, lipids). This chemical reaction is non-specific and irreversible. Even if the covalent bond is cleaved, the compound released will not be the highly reactive intermediate metabolite. The covalently bound metabolites can have a potential toxic effect in the target species but they probably represent low toxicity for consumers. Pharmacokinetic analyses of CBRs have demonstrated their specific properties: 1) they make up the largest fraction of late residues, and 2) their bioavailability is low. Several examples are given to support these concepts.
共价结合残基（CBRs）是母体药物或其代谢产物与内源性大分子共价结合的产物。它们不能通过彻底提取、变性和增溶技术从组织中提取出来，也不是内源性掺入的结果。在给予放射性标记药物后，它们可以在组织中持续存在的不可提取放射性中被检测到。本文讨论了CBRs的特性。共价结合是一种反应性代谢产物（亲电试剂或自由基）与内源性分子（蛋白质、脂质）的结合。这种化学反应是非特异性的且不可逆。即使共价键断裂，释放出的化合物也不会是高反应性的中间代谢产物。共价结合的代谢产物可能对目标物种具有潜在毒性作用，但对消费者来说可能毒性较低。对CBRs的药代动力学分析已经证明了它们的特殊性质：1）它们构成了晚期残留的最大部分，2）它们的生物利用度较低。文中给出了几个例子来支持这些概念。
