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Overview Phase I metabolism oxidation (via cytochrome P450), reduction, and hydrolysis reactions phase I reactions convert a parent drug to more polar (water soluble) active metabolites by unmasking or inserting a polar functional group (-OH, -SH, -NH2) geriatric patients have decreased phase I metabolism drugs metabolized via phase I reactions have longer half-lives geriatric patients metabolism drugs by phase II reactions Phase II metabolism glucuronidation, acetylation, and sulfation reactions conjugation reactions that increase water solubility of drug with a polar moiety glucuronate, acetate, and sulfate, respectively phase II reactions convert a parent drug to more polar (water soluble) inactive metabolites by conjugation of subgroups to -OH, -SH, -NH2 functional groups on drug drugs metabolized via phase II reactions are renally excreted patients deficient in acetylation capacity (slow acetylators) may have prolonged or toxic responses to normal doses of certain drugs because of decreased rates of metabolism What is Phase I Metabolism

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& Khalid, K.A

Biol Psych (2019) 85(11):90414

doi: 10.1073/pnas.1607571113 194 NaviauxRK