5 - Kinetics - ADME Flashcards
Describe the plasma concentration over time curve and it’s different components.
Plasma concentration (y) and Time (x). Initial absorption phase shows steep increase until reaching Cmax. Elimination phase uses half-lives to slowly reduce until plateau at Cmin (assuming 1st order).
Describe ADME for an oral drug
Ingest
- A -> Absorption in stomach
- D -> Distribution via circulation in blood stream
- M -> Liver containing enzymes that will metabolise drug into a different form. This can either be less, more, or equally effective.
- M -> Eliminated via kidneys
3 ways drugs can permeate cell membrane?
- Can diffuse through lipid bilayer
- Diffuse through aqueous channel
- Carrier
Describe how drugs enter the eye most of the time?
- What are the requirements of a drug in order to enter?
Cornea has lipophilic epithelium, hydrophilic stroma, and thin lipophilic endothelium. Epithelium has tight junctions. Drugs with log P > 2 and molecular weight of <5kDa can pass.
Describe how pKa affects drug permeability across cornea
- What’s pKa?
- Relation to cornea?
pKa governs how likely drug is ionised at different pHs. Example of homatropine with pKa of 9.7. Since body pH is 7, it is mostly unionised at pH7. This means it is lipophilic and can penetrate the epithelium but not the stroma.
Larger pKa then pH means more unionised form meaning more lipophilic.
How are prodrugs utilised for ocular drops?
We make ester prodrugs which have ester groups attached to them so that they are more lipophilic. They lose esters via enzymes in cornea which lets them become hydrophilic and pass the stroma easily.
Describe 1st and zero order
1st order is where half-life applies and drug concentration is halved after T1/2. 0 order occurs when elimination method can be saturated so large concentrations do not increase elimination rate. This presents a linear graph until reaching a concentration where 1st order applies.
How are drugs eliminated at the eye?
Lots of it leaves due to tears. Reflex tearing washes it away. Most drugs leave via nasolacrimal duct and a lot of drug is absorped by conjunctiva over sclera which takes it away via capillaries and back into blood so pointless.
