Effect of pH on drug absorption
After Drug Administration?Drug at site of administration
Drug in plasma
Drug/metabolites in urine, feces, bile
Drug/metabolites in tissues
1. Absorption
2. Distribution
4. Elimination
3. Metabolism
Note : All kinetic process involve transport of drug across biological membrane which are bilayer of phospholipids and cholesterol molecules.
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1.Transport : active or passive 2. pH 3. Physical factors: include blood flow surface area contact time
* Factors Affecting Drug Absorption
FACTORS AFFECT DRUG ABSORPTION
2. PH Drug are either weak acid or weak base Weak acid HA H+ + A- Weak base BH+ B+H+pH of the medication
The pH and pKa are the most important factors. The pH of the tissue determines the ratio of ionized to non-ionized drug. This ratio depends on the pKa of the drug. This amount will determine the easy with which the drug will penetrate or not through the tissues.Drugs pass through ,membrane more easy if it is uncharged (not ionized) i.e ((HA) for acid ) and ((B) for base) while charged (ionized ) can not passes
* the ratio between charged and uncharged is determined by PH at site of absorption and by the strength of acid and base i.e (pka) The lower pka of drug the stronger the acid ,conversely the higher pka the stronger the base
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Henderson Hasselbalch Equation
* e.g. in case of infection or inflammation low natural PH (acidic tissue) cause less effect of L.A (weak base). This acidity results in a greater proportion of the ionized (charged) form of the anesthetic, thereby delaying or preventing the onset of action. i:e the PH > pKa ( more drug in ionized form) e.g. acidic drug (aspirin) unionized at acid gastric PH and absorbed from stomach.Local anaesthetics are weak bases – proportion of free base (unionized)and salt (ionized) forms depends on pH and pK of amino grouppH - pK = antilog [base]/[salt](Henderson-Hasselbalch equation)pH - pKa = log [non-ionized /ionized] Example: Calculate the proportions of free base and salt forms of tetracaine (pKa = 8.5) at pH (7.5).
Local anaesthetics are weak bases – (Henderson-Hasselbalch equation)pH - pKa = log [non-ionized /ionized] Example: Calculate the proportions of free base and salt forms of tetracaine (pKa = 8.5) at pH (7.5).7.5 - 8.5 = antilog [base] unionized/[salt] (ionized) -1 = log [base] /[salt] 10-1 = 1/10 =[base]/[salt] ∴ there is 10x more drug in the ionized than (1) in the non-ionized form at physiological pH