pharmacokinetics

Three phases of drug action

1. Pharmaceutical: disintegration of pill in GI tract —> release of drug

2. Pharmacokinetic: absorption into blood supply, factors affecting drug’s survival to the target

3. Pharmacodynamic: drug interaction with molecular target

Absorption

• Drugs must cross cells lining gut wall (two fatty cell membranes)

• Need both hydrophilic and hydrophobic character

Lipinski’s rule of five

• MW < 500Da

• 5 HBD groups or less

• 10 HBA groups or less

• LogP value < +5

contributes to oral activity of drug (at least 3)

Distribution

• Drugs can quickly cross blood vessel walls through pores between cells

• First pass effect: % of absorbed drug deactivated by liver metabolism before distribution occurs

• Drug is distributed evenly throughout blood supply within 1 minute of absorption

Time to reach steady state

6 times the drug’s half life

Oral bioavailability

Fraction of ingested dose that survives to reach the blood supply

Barriers to drug distribution

• tight junctions that limit rapid paracellular diffusion of proteins and polar compounds (BBB, placental barrier)

• Plasma protein (albumin) can bind reversibly with drugs