Pharmacokinetics Overview PDF

CYP450 enzymes are crucial for drug metabolism and pharmacokinetic...

CYP450 enzymes are crucial for drug metabolism and pharmacokinetic interactions. Importance in Drug Interactions They can be inducers or inhibitors, Drugs can be excreted in feces, sweat, affecting drug concentrations and effects. saliva, and breast milk, though to a lesser extent. Inducers stimulate CYP isozymes, leading to increased metabolism of drugs. Understanding these pathways is Alternative Excretion Pathways important for assessing potential drug CYP Inducers This results in decreased plasma exposure to others. Cytochrome P450 Enzymes concentrations and potential loss of therapeutic effect. Certain populations, such as neonates or Excretion Routes Beyond those with liver disease, may have altered Kidneys P450 enzymes exhibit genetic excretion patterns. polymorphism, affecting drug efficacy and adverse events. Impact on Special Populations Adjustments in therapy may be necessary to prevent toxicity or therapeutic failure. Genetic Variability Variations can lead to differences in metabolism among individuals and populations. A loading dose may be used to quickly achieve desired plasma levels, followed by maintenance doses. Phase I involves the introduction or unmasking of polar functional groups. The maintenance dose is calculated based Maintenance and Loading Doses on clearance and target plasma Phase I Reactions Reactions include oxidation, reduction, concentration. and hydrolysis, often mediated by CYP enzymes. Individual patient factors, such as age, weight, and organ function, must be Phase II consists of conjugation reactions, considered in dosing. making drugs more water-soluble. Adjusting for Patient Variability Phase II Reactions Regular monitoring of drug levels helps These reactions typically result in inactive tailor therapy to achieve optimal outcomes. Dosage Regimen Design Drug Metabolism Phases metabolites that are easier to excrete. Pharmacokinetics Continuous infusion can lead to steady- state concentrations where drug Overview Phase I prepares drugs for Phase II by increasing polarity. administration equals elimination. Comparison of Phase I and Phase II Phase II focuses on conjugation, Continuous Infusion and Steady State The time to reach steady state is typically 4- enhancing elimination through renal or 5 half-lives of the drug. biliary routes. Most drugs follow first-order kinetics, The kidney plays a vital role in drug where a constant fraction is eliminated elimination through filtration and over time. secretion. First-Order Kinetics Renal Clearance This relationship allows for predictable Renal dysfunction can lead to drug dosing based on drug concentration. accumulation and increased risk of toxicity. Zero-order kinetics occurs when the The liver metabolizes drugs, contributing enzyme is saturated, leading to a constant significantly to overall clearance. amount of drug eliminated. Hepatic Clearance Hepatic blood flow and enzyme activity Zero-Order Kinetics Drug Clearance Mechanisms can influence drug metabolism rates. This can complicate dosing and requires careful monitoring of drug levels. Kinetics of Drug Metabolism Total clearance is the sum of renal and Drug interactions, genetic factors, and hepatic clearance. physiological conditions can alter metabolism kinetics. Total Body Clearance It is essential for determining appropriate dosing regimens for patients. Factors Affecting Kinetics Understanding these factors is crucial for optimizing therapeutic regimens.