5. (15 pts) Partition & Permeability. Prednisone is an anti-inflammatory corticosteroid that is converted by the liver t
Posted: Fri Mar 04, 2022 10:31 am
5. (15 pts) Partition & Permeability. Prednisone is an anti-inflammatory corticosteroid that is converted by the liver to an active drug form, prednisolone. To measure the ability of prednisolone to enter cells, researchers measure the partition coefficient (KD) between octanol and water. Following separation of the drug between organic and aqueous phases, they find prednisolone solubility in octanol is 7.5 mg/mL while solubility in the water is 1.92 mg/mL. OH OH OH OH 11-B-hydroxydehydrogenase Н Prednisone Active: Prednisolone a) (3 pts) Into which layer (water or octanol) does most of the drug preferentially partition? b) (3 pts) What is the calculated partition coefficient (KD)? c) (4 pts) Given the thickness of the cell membrane is 2.5 nm and the diffusion coefficient of prednisolone in the lipid bilayer is 6x10-7 cm?s', what is the permeability coefficient in units of cm/s? d) (5 pts) If previously untreated cells are in culture are exposed to media containing 5 uM prednisolone, what is the initial diffusion rate of drug into the cells in mol/s? The average cell diameter is 20 microns and the drug’s molecular weight is 360g/mol. You can assume the cells are in suspension, so they are roughly spherical and exposed to media on all sides.