Pharmacology 2060A/B Lecture Notes - Lecture 4: Prodrug, Active Metabolite, Lipophilicity

Experiment 8: Determination of k 45 Exp 8: Determination of Logkow Values for Four Drugs Objectives . Discover how compound polarity affects absorptiorn e Perform extractions Calculate and compare partition coefficients (Olog Kp)of four different pharmaceutical Intreduction Pharmaceutical drug design involves creating a molecule that will target a general region or site and have a therapeutic effect on the patient. Such properties depend on the drug's structure as well as its affinity for different phases in the body. When orally ingested, a drug moves from the stomach into the small intestine. From there, a drug must pass through a layer of cells before it can enter the bloodstrcam (this process is called absorption) and be distributed throughout the body. This requires crossing through largely non-polar cell membrane twice, first to enter the cell from the intestine side and then to exit the cell for entry into the bloodstream Solubility properties have a large influence on the drug's ability to navigate this trek. The drug must be polar enough to convey water solubility so that it does not precipitate out in the water solution that is well, us. For it to be absorbed into the bloodstream, however, a drug mast be non-polar enough to pass through a non-polar lipid bilayer that forms the membranes of cells. A lipid is an organic molecule that can be extracted from living tissues using non-polar organic solvents. A lipid bilayer is a thin membrane made of two lipid layers; the bilayer forms a spherical non-polar barrier separating the inside of a cell from the outside of a cell. The types of lipids that are found in cell membeanes (most commonly phospholipids (Figure 1)) are amphiphilic molecules consisting of hydrophobic ("water-fearing") and hydrophilic ("water-loving") parts. In lipid bilayers, these amphiphilic molecules arrange themselves such that the inside of the bilayer is hydrophobic while the outside (which faces the aqucous intracellular and extracellular environments) is hydrophilic (Figure 2) Figure 1: A phospholipid containing a hydrophilic head and two hydrophobic tails Figure 2: A cartoon representation ofa layer of cells separating the intestne from the bloodstream. An orally-ingested drug must pass through a cell to enter the Noodstream, cncountering both hydrophobic and hydrophilic environments in the process. Diffusion of Drug

Experiment 8: Determination of k 45 Exp 8: Determination of Logkow Values for Four Drugs Objectives . Discover how compound polarity affects absorptiorn e Perform extractions Calculate and compare partition coefficients (Olog Kp)of four different pharmaceutical Intreduction Pharmaceutical drug design involves creating a molecule that will target a general region or site and have a therapeutic effect on the patient. Such properties depend on the drug's structure as well as its affinity for different phases in the body. When orally ingested, a drug moves from the stomach into the small intestine. From there, a drug must pass through a layer of cells before it can enter the bloodstrcam (this process is called absorption) and be distributed throughout the body. This requires crossing through largely non-polar cell membrane twice, first to enter the cell from the intestine side and then to exit the cell for entry into the bloodstream Solubility properties have a large influence on the drug's ability to navigate this trek. The drug must be polar enough to convey water solubility so that it does not precipitate out in the water solution that is well, us. For it to be absorbed into the bloodstream, however, a drug mast be non-polar enough to pass through a non-polar lipid bilayer that forms the membranes of cells. A lipid is an organic molecule that can be extracted from living tissues using non-polar organic solvents. A lipid bilayer is a thin membrane made of two lipid layers; the bilayer forms a spherical non-polar barrier separating the inside of a cell from the outside of a cell. The types of lipids that are found in cell membeanes (most commonly phospholipids (Figure 1)) are amphiphilic molecules consisting of hydrophobic ("water-fearing") and hydrophilic ("water-loving") parts. In lipid bilayers, these amphiphilic molecules arrange themselves such that the inside of the bilayer is hydrophobic while the outside (which faces the aqucous intracellular and extracellular environments) is hydrophilic (Figure 2) Figure 1: A phospholipid containing a hydrophilic head and two hydrophobic tails Figure 2: A cartoon representation ofa layer of cells separating the intestne from the bloodstream. An orally-ingested drug must pass through a cell to enter the Noodstream, cncountering both hydrophobic and hydrophilic environments in the process. Diffusion of Drug