Pharmacokinetics

    Cards (6)

    • The drug concentration at the target site is the concentration that determines whether the drug is effective. However, in pharmacokinetics we are usually most interested in the plasma concentration.
      Drugs are distributed around the body in the plasma. From the plasma they move into the tissues or to sites of metabolism or excretion. Importantly, it is the plasma concentration to which we have easiest access for measurement
    • The plasma concentration of a drug can change over time. Following a single intravenous (i.v.) bolus injection, the plasma concentration is initially high then decreases. The timecourse of this decrease is affected by distribution, metabolism and excretion of the drug. Following a single oral dose, the plasma concentration initially increases owing to drug absorption, before decreasing as metabolism and excretion increase.
    • The plasma concentration of a drug must be higher than the minimum effective concentration to see the desired therapeutic effect
      If the concentration is too high, toxic effects may be seen. The gap between the minimum effective concentration and the minimum toxic concentration is called the therapeutic window. Ideally, the therapeutic window will be as wide as possible. An effective dosing strategy will maintain the plasma concentration within the therapeutic window for as long as necessary.
      • Tissues in the body can be considered as a series of aqueous compartments, separated by membrane or cellular barriers that restrict movement of molecules including drugs.
      • The plasma is a compartment. Unless the target is in the plasma, the drug must leave the plasma and enter the interstitial compartment by crossing the endothelium
      • In the interstitial compartment the drug can act on interstitial targets or on cellular targets that are exposed
      • If a drug needs to act on an intracellular target (such as nuclear receptors or metabolic enzymes), the drug must cross the plasma membrane
      • Transcellular compartments are protected by specialised barriers. For example, the cerebrospinal compartment is behind the blood-brain barrier.
      • The rate of diffusion of a drug across a cell membrane is highest or highly lipophilic drugs, whereas charged or highly polar drugs diffuse poorly
      • The rate of diffusion also depends on the concentration gradient and the surface area of membrane
      • Many drugs are weak bases or acids and appear in solution as both an ionised and an un-ionised form. The un-ionised form is usually more lipid soluble so diffuses readily, whereas the ionised form cannot cross the membrane.
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