Partition coefficient & bioavailability

Partitioning

Distribution of a substance between two immiscible phases

Partition coefficient (P)

Ratio of concentration in organic phase to aqueous phase

What does high P mean

Drug is lipophilic

What does low P mean

Drug is hydrophilic

Log P

Logarithmic measure of lipophilicity

Why use log P

Simplifies large range of P values

Which phases are commonly used

Octanol and water

Why octanol is used

Mimics biological membranes

What is apparent partition coefficient (Papp)

Partition coefficient including ionised species

Why P is not constant for drugs

Ionisation creates multiple species

What determines Papp

Degree of ionisation (depends on pH and pKa)

What is fraction unionised

Proportion of drug in non-ionised form

Relationship

Papp = P × fraction unionised

pH-partition hypothesis

Only non-ionised drugs cross membranes

Why balance is important

Drugs need both aqueous solubility and lipophilicity

Where drug absorption mainly occurs

Small intestine

Why small intestine is ideal

Large surface area, long residence time, good blood supply

Limitation of pH-partition theory

Ionised drugs can still be absorbed

What is ion pairing

Ionised drug forms neutral complex to cross membrane

What is active transport

Energy-dependent absorption of molecules

Example of drug using active transport

Melphalan