The Effect of Cytochrome P450 Metabolism on Drug Response, Interactions, and Adverse Effects¶
Lynch, T., & Price, A. (2007). The Effect of Cytochrome P450 Metabolism on Drug Response, Interactions, and Adverse Effects. American Family Physician.
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Domain-specific¶
- Pharmacokinetic Interaction
- The mechanism is structured by the four ADME stages, each with its own drug-interaction class. Absorption interactions: an antacid chelating a fluoroquinolone antibiotic in the gut, or food delaying gastric emptying and thereby flattening a drug's absorption peak. Distribution interactions: protein-binding displacement, in which one agent displaces another from plasma albumin or alpha-1-acid glycoprotein, transiently raising free (active) drug concentrations. Metabolism interactions, the most clinically consequential class: inhibition or induction of hepatic and intestinal cytochrome P450 enzymes (most prominently CYP3A4, CYP2C9, CYP2D6) alters the rate at which drugs are chemically transformed
This sourceClinical review of cytochrome P450 metabolism reporting that these enzymes are expressed in liver and small intestine and that drugs can inhibit or induce them, altering how fast co-administered drugs are metabolised and producing clinically significant interactions.
Supported in partVerified against the work's full text
“Cytochrome P450 enzymes can be inhibited or induced by drugs, resulting in clinically significant drug-drug interactions that can cause unanticipated adverse reactions or therapeutic failures.”
- The mechanism is structured by the four ADME stages, each with its own drug-interaction class. Absorption interactions: an antacid chelating a fluoroquinolone antibiotic in the gut, or food delaying gastric emptying and thereby flattening a drug's absorption peak. Distribution interactions: protein-binding displacement, in which one agent displaces another from plasma albumin or alpha-1-acid glycoprotein, transiently raising free (active) drug concentrations. Metabolism interactions, the most clinically consequential class: inhibition or induction of hepatic and intestinal cytochrome P450 enzymes (most prominently CYP3A4, CYP2C9, CYP2D6) alters the rate at which drugs are chemically transformed
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