PH - Partition Theory (w25) Flashcards
What does the pH-partition theory state ?
pH-partition theory states that the absorption of weak acids and bases is determined by the degree of ionisation, i.e. Henderson-Hasselbalch equation
What does the gastro-intestinal epithelium acts as to drug absorption ?
A lipoidal barrier
Where is a weak base more likely to be absorbed ?
In the small intestine
How are the small intestines better designed for absorption in comparison to the stomach ?
- Surface area of the small intestines is up to 200 m2 as a result of microvilli
- Drugs have a longer residence time in the small intestines than the stomach
- Small intestines have an excellent blood supply
What factors determine the absorption from the GI tract ?
- Molecular weight
- Lipid solubility (log P often used as a proxy)
- Water solubility
- Binding to Ca2+, Mg2+, Al3+ present in milk, antacids etc.
- Ion-pairing
- Presence of active transport mechanisms
What is ion-pairing ?
Ion-pairing is when oppositely charged ions are held together without the formation of a covalent bond
What d the ion-pair behave as ?
The ion-pair behave as a neutral species and may be better able to permeate the gastric mucosa
What is melphalan ?
Melphalan is an anti-cancer drug indicated for several conditions including multiple myeloma
What three parameters determine the degree of drug distribution into breast milk ?
- pKa of drug (milk has a mean pH of 7.2)
- Degree of plasma protein binding
- Log P of drug (milk fat content varies from 4 – 9%)
During drug excretion, what happens if the unionised form of a drug is favoured ?
If unionised form is favoured, the molecule may be reabsorbed back into the circulation by passing back through the lipid membrane in Loop of Henle
Drug re-enters the circulatory system, free to exert its therapeutic action again
How can renal excretion of drugs be controlled ?
Renal excretion of drugs can be controlled by altering the pH of the urine with salt solutions, e.g. sodium citrate which is urine alkaliniser
