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Pharmacokinetics in Obese Patients: Drug Metabolism and Excretion01:20

Pharmacokinetics in Obese Patients: Drug Metabolism and Excretion

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Drug metabolism, a critical process in the liver, involves two primary phases: Phase I reactions and Phase II conjugation. Obesity introduces significant alterations in this metabolic process, primarily due to fatty infiltration of the liver, leading to conditions such as nonalcoholic fatty liver disease (NAFLD). This condition can modify the activities of both Phase I and II enzymes, impacting how drugs are metabolized in obese patients.Phase I metabolism sees variable effects across...
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Drug Metabolism: Phase I Reactions01:17

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A phase I reaction is a biochemical process that introduces a functionally reactive polar group to a substance. This transformation predominantly occurs in the liver, facilitated by the cytochrome P450 system of hemoproteins situated in the lipophilic endoplasmic reticulum of cells. The metabolite generated through this process can have varying polarities. If it is sufficiently polar, it can be easily excreted in the urine due to its water compatibility. However, if the metabolite is nonpolar,...
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Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance01:23

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The elimination half-life and drug clearance of drugs following nonlinear kinetics can vary with dosage. The Michaelis-Menten parameters and drug concentration influence these factors. As the dose increases, the elimination half-life tends to lengthen, resulting in a reduction in clearance and a disproportionately larger area under the curve. The total clearance can be derived from the Michaelis-Menten equation for drugs following a one-compartment model.
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Enterohepatic cycling involves the active secretion of drugs and their metabolites into the bile via transporters in the canalicular membrane of hepatocytes. This secretion is an integral part of the digestive process, releasing these substances into the gastrointestinal (GI) tract.
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Drug Metabolism: Phase II Reactions01:14

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Phase II reactions are essential for the detoxification and elimination of drugs from the body. These reactions involve the conjugation of parent drugs or their phase I metabolites with endogenous molecules, resulting in more hydrophilic drug conjugates. The primary conjugation reactions in this phase are sulfation and glucuronidation. Both sulfation and glucuronidation typically produce biologically inactive metabolites. However, in some cases involving prodrugs, active metabolites may be...
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Pharmacogenetics of Drug Metabolism: Overview01:27

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Genetic polymorphism in drug metabolism is crucial to the inter-individual variability observed in drug responses. Drug metabolism primarily involves the chemical modification of drugs and other xenobiotics to enhance their elimination by increasing their polarity. Two main classes of enzymes mediate this biotransformation process: Phase I enzymes, primarily cytochrome P450s, catalyze oxidation and reduction reactions, while other enzymes, such as esterases, mediate hydrolysis, and Phase II...
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Updated: Feb 25, 2026

A Protocol for Measuring Cue Reactivity in a Rat Model of Cocaine Use Disorder
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Metabolism, Not Mendacity: Rethinking Prolonged Cocaine Positivity.

Daniel M Bowen, Maryam Soltani

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    Summary
    This summary is machine-generated.

    Prolonged cocaine metabolite detection in urine toxicology can be due to metabolic variability, not relapse. Understanding pharmacogenomic factors and liver function is crucial for accurate interpretation in addiction treatment.

    Keywords:
    cocainemetabolismpharmacogenomicspharmacokineticstherapeutic alliance

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    Area of Science:

    • Pharmacogenomics
    • Addiction Medicine
    • Clinical Toxicology

    Background:

    • Urine toxicology is vital for monitoring substance use disorder treatment.
    • Standard detection windows may not reflect individual metabolic variability.
    • Misinterpreting prolonged positivity as relapse can harm patient treatment.

    Purpose of the Study:

    • To highlight how metabolic variability can cause prolonged cocaine metabolite detection.
    • To emphasize the importance of considering pharmacokinetic factors in toxicology.
    • To advocate for patient-centered interpretation of urine drug screens.

    Main Methods:

    • Case report of a patient with stimulant use disorder and prolonged cocaine metabolite positivity.
    • Laboratory evaluation including hepatic steatosis assessment.
    • Pharmacogenomic testing revealing CYP2D6 and CYP3A5 poor metabolizer phenotypes.

    Main Results:

    • Cocaine metabolites remained positive for 18 days, 12 days after verified abstinence.
    • Patient exhibited poor metabolizer phenotypes for CYP2D6 and CYP3A5.
    • Monotonic decline in metabolite levels suggested delayed elimination, not recurrent use.

    Conclusions:

    • Impaired CYP450 enzyme activity, hepatic steatosis, and stimulant use can prolong cocaine metabolite clearance.
    • Distinguishing biological variability from relapse is essential for therapeutic rapport.
    • Consider pharmacogenomic variation and liver function in cases of unexpected persistent positivity.