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PharmD clinical pharmacy program Level 3, Semester 2 Biopharmaceutics & Pharmacokinetics (PT608(

4. Regional Differences in Physiologic pH

 According to the pH-partition hypothesis, basic drugs present in blood (pH 7.4)

readily enter into acidic tissues and fluids, including the intracellular fluids

(pH 7.0) and concentrate there. The difference in pH can lead to localization of

drug in tissues and fluids.

✓ A drug that is predominantly in its ionized state at physiologic pH (7.4)

✓ Does not readily cross membrane barriers and

✓ Probably has a limited distribution

Example of this phenomenon

Excretion of drugs in breast milk

 Only un-ionized drug can pass through lipid membrane
barriers into breast milk.
 Alkaline drugs, which would be mostly un-ionized at pH 7.4,

pass into breast tissue.

Once in breast tissue, the alkaline drugs ionize because breast tissue
has an acidic pH; therefore, the drugs become trapped in this tissue

 N.B. The pH of milk is slightly acidic (pH6.5 to 6.8) to the

blood).
 This same phenomenon can occur in the urine.

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