Partition Coefficient Definition:
- The partition coefficient (P) is the ratio of a drug’s solubility in lipid (oil) vs. water.
- It is often expressed as log P, which quantifies lipophilicity.
- $P = \frac{\text{Concentration in lipid phase}}{\text{Concentration in aqueous phase}}$
- High log P (>3): Lipophilic (fat-soluble)
- Low log P (<1): Hydrophilic (water-soluble)
- Optimal log P (~1-3): Good balance between solubility and membrane permeability
Importance in Drug Action:
- Absorption: Lipophilic drugs pass through membranes easily (high log P).
- Blood-Brain Barrier (BBB): Only lipophilic drugs (log P > 2) cross the BBB effectively.
- Protein Binding: Highly lipophilic drugs tend to bind strongly to plasma proteins.
- Metabolism: Lipophilic drugs often require metabolic conversion (Phase I & II) before excretion.
- Excretion: Hydrophilic drugs are excreted in urine, while lipophilic drugs are excreted in bile.
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Examples of Partition Coefficient:
- High log P (e.g., diazepam, THC): Easily penetrate the brain.
- Low log P (e.g., aminoglycosides): Poor cell membrane penetration.
Biological Impact:
- Membrane Permeability: Drugs with an optimal log P (often between 1 and 3 for many orally active drugs) can effectively cross lipid membranes.
- Distribution and Clearance: Highly lipophilic drugs may accumulate in fatty tissues and have a longer half-life, while very hydrophilic drugs may be rapidly cleared.
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