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Updated: Mar 28 2022


  • Volume of Distribution (Vd)
    • Volume of distribution (Vd) relates amount of drug in body to plasma concentration
    • Vd = (amount of drug in the body) / (plasma drug concentration)
    • Vd is changed in disease states that decrease plasma proteins
      • a decrease in plasma proteins decreases binding of drug to plasma proteins
        • ↑ Vd of drugs
      • e.g., liver disease
        • via ↓ protein synthesis
      • e.g., kidney disease
        • via urinary protein loss
    • Vd increased in disease states that increase total body water
      • ascites, pulmonary edema, heart failure
      • can lower plasma concentration of water soluble drugs
    • Vd predicts drug distribution in body
      • low Vd drugs
        • 4-8 L
        • drugs distribute in vascular compartment (blood) and bind plasma proteins
        • drugs are large and/or charged molecules
      • medium Vd drugs
        • drugs distribute in extracellular compartment and/or total body water
        • drugs are small, hydrophilic molecules that do not bind plasma proteins
      • high Vd drugs
        • > body weight
        • drugs distribute in all tissues
        • drugs are small, lipophilic molecules that bind strongly to extravascular proteins
  • Clearance (CL)
    • CL = (rate of elimination of drug) / (plasma drug concentration) = Vd * Ke
      • Ke = elimination constant
    • CL relates the rate of elimination to the plasma concentration
  • Half-Life (t1/2)
    • t1/2 = (0.7 * Vd)/CL
    • half-life is time required for amount of drug to fall to 50% of an earlier measurement during elimination or during constant infusion
      • a drug infused at a constant rate reaches about 94% of steady state after 4 half lives
    • for drugs eliminated by first-order kinetics, half-life is constant regardless of concentration
      • # of half lives
      • 1
      • 2
      • 3
      • 4
      • Concentration
      • 50%
      • 75%
      • 87.5%
  • Bioavailability (F)
    • bioavailability is the fraction of administered dose that reaches systemic circulation
    • bioavailability is defined as unity, or 100%, in case of IV administration
    • bioavailability of drug administered by other routes is generally reduced by incomplete absorption, first-pass metabolism, and any distribution into other tissues that occurs before the drug enters systemic circulation
      • e.g., orally, F = percent that is absorbed and survives first-pass metabolism in liver
    • Calculation of bioavailabillity (F) = 100% * (AUC-oral * Dose-IV) / (AUC-IV * Dose-oral), where AUC is the area under the curve of a pharmacokinetic plasma concentration versus time plot
    • delayed release formulations will have slower rise and lower peak compared with rapid release formulations
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