Nursing Pharmacology Chapter 2:  General Principles:  Pharmacokinetics

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"Introduction to Pharmacokinetics"



Some Factors Influencing Absorption and Bioavailability

Fick's Law

  •  Fick's Law describes passive movement molecules down its concentration gradient.

Flux  (J) (molecules per unit time) = (C1 - C2) · (Area ·Permeability coefficient) / Thickness

  1. Where C1 is the higher concentration and C2 is the lower concentration

  2. Area = area across which diffusion occurs

  3. Permeability coefficient: drug mobility in the diffusion path

    • For lipid diffusion, lipid: aqueous partition coefficient -- major determinant of drug mobility

      • Partition coefficient reflects how easily the drug enters the lipid phase from the aqueous medium.

  4. Thickness: length of the diffusion path

  • Katzung, B. G. Basic Principles-Introduction , in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, p 5.


Henderson-Hasselbalch equation

General Form:  log (protonated)/(unprotonated) = pKa - pH

  • For Acids: pKa = pH + log (concentration [HA] unionized)/concentration [A-]

    • note that if [A-] = [HA] then pKa = pH + log (1) or (since log(1) = 0), pKa = pH

  • For Bases: pKa = pH + log (concentration [BH+] ionized)/concentration [B]

    • note that if [B] = [BH+] then pKa = pH + log (1) or (since log(1) = 0), pKa = pH

  1. The lower the pH relative to the pKa the greater fraction of protonated drug is found.  Recall that the protonated form of an acid is uncharged (neutral); however, protonated form of a base will be charged.

  2. As a result, a weak acid at acid pH will be more lipid-soluble because it is uncharged and uncharged molecules move more readily through a lipid (nonpolar) environment, like the some membrane,  than charged molecules

  3. Similarly, a weak base at alkaline pH will be more lipid-soluble because at alkaline pH a proton will dissociate from molecule leaving it uncharged and again free to move through lipid membrane structures

Drugs that are weak acids or bases

Weak acids


Weak bases


  • Phenobarbital (Luminal)


  • Cocaine


  • Pentobarbital (Nembutal)


  • Ephedrine


  • Acetaminophen


  • Chlordiazepoxide (Librium)


  • Aspirin


  • Morphine





  • Figure Developed by Dr. Steve Downing, University of Minnesota


Extent of Absorption

Ion Trapping

Ion Trapping: Placental transfer of basic drugs

  • Placental transfer of basic drugs from mother to fetus: local anesthetics.

  • Fetal pH is lower than maternal pH.

  • Lipid-soluble, nonionized local anesthetic crosses the placenta converted to poorly lipid-soluble ionized drug.

    •  Drug gradient is maintained for continual transfer of local anesthetic from maternal circulation to fetal circulation.

    •  In fetal distress, acidosis contributes to local anesthetic accumulation.