Читать книгу Physiologically Based Pharmacokinetic (PBPK) Modeling and Simulations - Sheila Annie Peters - Страница 33

Certain drugs like Tetrahydrocannabinol (THC) and morphine are metabolized to active metabolites (11‐hydroxy‐THC and morphine‐6‐glucuronide, respectively) with pharmacological activity that can be significant. Codeine and tramadol have metabolites (morphine and O‐desmethyltramadol respectively) that are stronger than the parent drug. Metabolites may also produce toxic effects, requiring patient monitoring to ensure they do not accumulate in the body. Metabolites may compete with the parent compound for the same plasma protein binding site, resulting in changes to the disposition of the parent drug. They may also inhibit or induce enzymes that metabolize the parent drug, causing changes to the exposure of the parent drug. The extent of metabolite activity, toxicity, displacement, or interaction depends on its concentration. Thus, examination of metabolite kinetics following drug administration plays a key role in characterizing its relevance for these processes.