The Biochemistry of Drug Metabolism – An Introduction

Abstract

This review on intra-individual factors affecting drug metabolism completes our series on the biochemistry of drug metabolism. The article presents the molecular mechanisms causing intra-individual differences in enzyme expression and activity. They include enzyme induction by transcriptional activation and enzyme inhibition on the protein level. The influencing factors are of physiological, pathological, or external origin. Tissue characteristics and developmental age strongly influence enzyme-expression patterns. Further influencing factors are pregnancy, disease, or biological rhythms. Xenobiotics, drugs, constituents of herbal remedies, food constituents, ethanol, and tobacco can all influence enzyme expression or activity and, hence, affect drug metabolism.

A Review on Cyclamen Species: Transcription Factors vs. Pharmacological Effects

“…Thus, each ethnic group can consume with reasonable security the products of their geographic area, previously selected over generations, but the same is false when they cross ethnicities and consume products of different origins. Depending on the time point when a mutation occurred in the history of mankind, particular mutations may be unique for a certain population or show differences in their frequency when comparing ethnicities, leading to population-specific responses to drugs and other xenobiotics (100).…”

SwissPKcdw – A clinical data warehouse for the optimization of pediatric dosing regimens

“…[1][2][3] For example, some drug-metabolizing enzymes reach adult levels shortly after birth, whereas others remain at lower activity for months to years. 4 In consequence, one drug may be metabolized at a similar rate as in adults, whereas another remains unchanged much longer in pediatric patients and accumulates with multiple doses. To give another example, renal excretion is disproportionately low until 2 years of age, affecting the half-life of drugs which are mainly renally excreted in adults.…”

“…To give another example, renal excretion is disproportionately low until 2 years of age, affecting the half-life of drugs which are mainly renally excreted in adults. 4,5 Pediatric drug development and drug use have significantly changed over the last 50 years from "therapeutic orphans," 6 to a situation where a robust regulatory framework has been created to ensure that new drugs are reviewed for potential use in pediatric patients. 7 But there is still a gap in information on drug use in pediatric patients and the information on pediatric use in the drug labels is still scarce, especially for drugs already approved, which leads to immense off-label usage in this patient population.…”

“…Most clinical trials were limited to adults, for practical and economic reasons and, consequentially, the differences in requirements for pediatric and adult patients are not visible 1–3 . For example, some drug‐metabolizing enzymes reach adult levels shortly after birth, whereas others remain at lower activity for months to years 4 . In consequence, one drug may be metabolized at a similar rate as in adults, whereas another remains unchanged much longer in pediatric patients and accumulates with multiple doses.…”