Medical Pharmacology Chapter 2: General Principles: Pharmacokinetics

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Pharmacokinetics and some IV Anesthetics Agents



  • 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 

    • Lipophilic and Hydrophilic Drugs

    • 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.

        • The pH and drug pKa determine the ratio of lipid-to aqueous-soluble forms for weak acids and bases as 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. 

        1. 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 cell membrane,  compared to 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 thus free to move through lipid membrane structures



  • Lipid diffusion depends on adequate lipid solubility

    • Drug ionization (charged form) reduces a drug's ability to cross a lipid bilayer.

  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