Intro to Pharmacokinetics

• Pharmacokinetics examines how the concentration of a drug in different body locations changes with given doses or routes
• Pharmacokinetics predicts human exposure from a planned dosage
• pharmacokinetics is important for therapeutic drug monitoring
• The therapeutic window is the plasma concentration above the lowest effective concentration and below the toxic concentration
• Therapeutic index provides a measurement of a drug's safety
• Clearance units:


  L/h
• Volume of distribution units:


  L or L/kg
• Half life units:


  h
• Cmax units:


  ug/mL
• Cmax refers to the highest drug concentration achieved
• Tmax units:


  h
• Tmax refers to the time taken for the drug to reach its
• AUC0-x units 


  ug.h/mL
• AUC0-x refers to the total drug exposure over time
• Bioavailability units:


  %
• Bioavailability refers to how much of an oral dose enters the blood
• Clearance describes the efficiency of drug elimination
• Clearance is measured as volume of blood cleared per unit time
• Elimination rate is proportional to the drug's concentration in the plasma
• Clearance determines maintenance dose rate
• Clearance is usually determined experimentally from AUC following IV administration
• Volume of distribution relates the amount of drug in the body to its concentration in the plasma
• Volume of distribution indicates the extent of distribution
• Volume of distribution is used to calculate the loading dose
• Volume of distribution is back-calculated from the initial drug concentration in the plasma following a given IV dose
• Drugs with high lipophilicity can cross membranes and have high Vd
• Hydrophilic drugs are trapped in the plasma and have low Vd
• Half-Life is the time required to halve the amount of drug in the body
• k = elimination rate constant
• k is determined by clearance and volume of distribution
• Drug elimination is usually exponential, following first order kinetics
• • Doubling the dose will only increase the drug's effects by one half-life
• Clearance determines the steady state drug concentration resulting from a maintenance dose rate
• Zero order kinetics: Proceeds at a constant rate; the drug will be metabolised until it is completely removed
• First order kinetics: The drug is eliminated as fast as possible, regardless of its concentration
• The net rate of change of drug is the rate of absorption minus the rate of elimination
• Bioavailability is the difference between plasma concentrations following an oral dose and an injection of the same amount
• Concentration of the drug in the body peaks when absorption is the same as elimination
• Concentration of the drug in the body rises when absorption is greater than elimination
• Concentration of the drug in the body falls when elimination is greater than absorption