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Drug Metabolism & Pharmacokinetics

There are a number of physiological barriers that exist in vivo, which reduce the amount of dosed compound that reaches the target. Therefore a drug candidate should possess properties that enable good absorption, distribution, low metabolism, reasonable elimination (ADME) and low toxicity in order to reach these targets. Good absorption is attributed to dissolution rate and solubility in the gastrointestinal tract. First pass metabolism occurs here followed by metabolism in the liver. Distribution happens when the compound permeates into the tissues from the blood capillaries, with elimination occurring simultaneously by removal of the compound from the bloodstream by the liver and the kidneys.

Efficient ADME processes can be determined by:

  • Physicochemical properties - solubility, permeability, lipophilcity, chemical stability
  • Pharmacokinetic properties - clearance, half-life, bioavailability, drug-drug interactions, LD50
  • Biochemical - metabolism, protein and tissue binding, and transport