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How does the liver metabolize the commonly prescribed drug, ibuprofen, and what are the specific enzymes involved in its breakdown?

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Ibuprofen is a nonsteroidal anti-inflammatory drug  NSAID  commonly prescribed for pain relief, reducing inflammation, and lowering fever. The liver plays a crucial role in the metabolism of ibuprofen, as it does with many other drugs.The primary enzymes involved in the metabolism of ibuprofen are the cytochrome P450  CYP  enzymes, specifically CYP2C9 and CYP2C8. These enzymes are responsible for the biotransformation of ibuprofen into its major metabolites.The metabolism of ibuprofen in the liver occurs through two main pathways: hydroxylation and carboxylation.1. Hydroxylation: In this pathway, the CYP2C9 enzyme catalyzes the formation of 2-hydroxyibuprofen and 3-hydroxyibuprofen. These hydroxylated metabolites are then further metabolized by other enzymes, such as uridine diphosphate glucuronosyltransferases  UGTs , which conjugate the hydroxylated metabolites with glucuronic acid to form glucuronide conjugates. These conjugates are more water-soluble and can be easily excreted from the body through urine.2. Carboxylation: In this pathway, the CYP2C8 enzyme catalyzes the formation of carboxyibuprofen. This metabolite is also conjugated with glucuronic acid by UGT enzymes to form a glucuronide conjugate, which can be excreted through urine.In addition to these primary pathways, a small fraction of ibuprofen undergoes other minor metabolic reactions, such as the formation of acyl glucuronides and oxidative metabolites.Overall, the liver plays a vital role in the metabolism of ibuprofen, with CYP2C9 and CYP2C8 enzymes being the primary catalysts for its biotransformation. The resulting metabolites are then further processed and excreted from the body, mainly through urine.
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