Producción CyT
Drug Metabolism Functionalization (Phase I) Reactions
Capítulo de Libro
Fecha:
2021Editorial y Lugar de Edición:
Springer Nature Switzerland AGLibro:
The ADME Encyclopedia. A Comprehensive Guide on Biopharmacy and Pharmacokinetics (pp. 1-7)Springer Nature Switzerland AG
ISBN:
978-3-030-51519-5Resumen
Functionalization (or Phase I) reactions of drug metabolism are those that introduce a functional drug to their substrates (for instance, in hydroxylation) or modify an existing one (e.g., in hydrolysis). The term functionalization is sometimes preferred to Williams’ classic Phase I denomination. Williams’ nomenclature reflects the usual scheme of sequential metabolism, where the parent drug is converted to a primary, or first-generation, metabolite, which in turn is subjected to a second biotransformation reaction that yields a secondary, or second-generation, metabolite. Whereas it is true that functionalization reactions often “prepare” their substrate to undergo a conjugation (Phase II) reaction (because they provide the substrate with a chemical “anchor” site for a conjugation to occur, such as a -OH or a -NH function), there are many deviations from this too general scheme. For instance, many Phase I metabolites are excreted without experiencing Phase II reactions. Similarly, the intact drug may directly undergo a Phase II transformation without a previous Phase I reaction. A drug may undergo one or more subsequent Phase I reactions before being conjugated (see Fig. 1 for figures). Finally, drug metabolism tends to operate in parallel and not only serially, since many different biotransformations occur simultaneously to different drug molecules of the same compound.Palabras Clave
DRUG METABOLISMCYPSCYP450CLEARENCE