Non-Cytochrome P450 Enzymes and Extra-Hepatic Drug Metabolism: Challenges and Opportunities

Drug biotransformation is a major factor for interindividual variability in drug response with direct impacts on the efficacy and safety of drugs. The prediction of cytochrome P450(CYP) activity, primarily in the liver, have contributed to decreased pre-market attrition rates. Therefore, there is an increasing number of new drugs that rely on non-Cyp enzymes for metabolism and elimination. However, the contribution of extrahepatic and non-CYP metabolic transformations have so far been poorly investigated. This special issue focuses on recent developments, challenges and opportunities posed by non-CYP metabolic pathways. In fact, predictive models for non-CYP and extrahepatic drug metabolism and pharmacokinetics are needed. Considerable efforts must be made towards the implementation of precision medicine strategies, including non-Cyp pharmacogenomics and metabolite phenotyping approaches. The Topic Editors have happy to receive manuscripts related to topics including but not restricted to:

· Phase II conjugation such as sulfonation, acetylation and glucuronidation

· other conjugation reactions with amino acids and proteins

· dehydrogenase-mediated oxidations,

· glutathione and glutathionyl radical conjugations

· extrahepatic drug metabolism by human- and microbiome-encoded metabolic pathways

· the impact of the intracellular localization on drug biotransformation,

· new models and analytical methodologies to study drug metabolism