Chapter 2: General Principles: Pharmacokinetics

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Pharmacokinetics and some IV Anesthetics Agents



Some Factors Influencing Absorption and Bioavailability


Absorption Principles:


"Absorption Overview"


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.

  • Plasma protein-bound drugs cannot permeate through aqueous pores

  • Charged drugs will be influenced by electric field potentials {membrane potentials, important in renal, trans-tubular transport}

  • II. Lipid diffusion 

    • Most important barrier for drug permeation due to:

      • many lipid barriers separating body compartments

    • Lipid: aqueous drug partition coefficients described the ease with which a drug moves between aqueous and lipid environments

    • Ionization state of the drug is an important factor: charged drugs diffuse-through lipid environments with difficulty.

      •  pH and the drug pKa, important in determining the ionization state, will influence significantly transport (ratios of lipid-to aqueous-soluble forms for weak acids and bases described by the Henderson-Hasselbalch equation.

        • uncharged form: lipid-soluble

        • charged form: aqueous-soluble, relatively lipid-insoluble (does not pass biological membranes easily)


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

  • Lipid diffusion depends on adequate lipid solubility

    • Drug ionization reduces a drug's ability to cross a lipid bilayer.

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






  1. Stoelting, R.K., "Pharmacokinetics and Pharmacodynamics of Injected and Inhaled Drugs", in Pharmacology and Physiology in Anesthetic Practice, Lippincott-Raven Publishers, 1999, 1-17.

  2. Dolin, S. J. "Drugs and pharmacology" in Total Intravenous Anesthesia, pp. 13-35 (Nicholas L. Padfield, ed), Butterworth Heinemann, Oxford, 2000