Pharmacokinetics (ADME)

Absorption, distribution, metabolism, and excretion are the four pillars that govern the pharmacokinetics of drugs. This chapter discusses lipophilicity, hydrogen bonding, polar surface area, and number of rotatable bonds, then the famous rule of 5, followed by ligand efficiency and lipophilic ligand efficiency. Aside from water and most hydrophilic drugs, all other molecules/drugs are metabolized. Renal excretion is the major route of elimination for hydrophilic drugs. Metabolism is key for bioactivation of prodrugs, which are inactive as such and need conversion in the body (i.e., metabolism) to one or more active metabolites. Prodrugs may offer certain advantages. Their active forms may be more stable; they can have better bioavailability, or other desirable pharmacokinetic properties or less side effects and toxicity. The distribution of a drug into intravascular, interstitial/tissue, and intracellular compartments is dictated by its physical and chemical properties.