+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Fundamental properties of local anesthetics. I. The dependence of lidocaine's ionization and octanol:buffer partitioning on solvent and temperature



Fundamental properties of local anesthetics. I. The dependence of lidocaine's ionization and octanol:buffer partitioning on solvent and temperature



Anesthesia and Analgesia 66(2): 159-165



The protonation equilibrium and hydrophobic character of lidocaine were characterized by its pKa and the octanol:buffer partition coefficients of the charged (P+) and neutral (Po) drug species. These measurements were accomplished by ultraviolet spectrophotometry of pure lidocaine HCl solutions at different temperatures, ionic strengths, and buffer concentrations. Corroboration of the pKa determination by the potentiometric method and of the partition coefficients by gas chromatography validated the general application of the spectrophotometric technique. The pKa increased with decreasing temperature (7.61 +/- 0.06 at 36 degrees C; 7.94 +/- 0.04 at 26 degrees C, in water; mean +/- SD), increasing ionic strength (8.06 +/- 0.02 at 26 degrees C in 0.165 M NaCl) and increasing buffer capacity (8.28 +/- 0.06 at 25 degrees C in 0.15 M NaCl + 20 mM buffer). Octanol:buffer partition coefficients for both the protonated and the neutral species (expressed as mole fractions) increased upon warning: 0.55 +/- 0.04 and 2666 +/- 202, respectively, at 25 degrees C, and 0.75 +/- 0.09 and 3210 +/- 272, respectively, at 36 degrees C. Ionic strength and buffer concentration had no significant effect on either P value. The increase in pKa at lower temperatures coupled with the decreased partition coefficients resulted in a nearly constant concentration of the protonated species in octanol as the system was cooled, whereas the concentration of the neutral species fell by more than 80%. This finding may explain the large increase in the impulse blocking potency of lidocaine observed upon nerve cooling, if the protonated anesthetic species is the more active form of the drug competing with the neutral species for a common binding site.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 040184755

Download citation: RISBibTeXText

PMID: 3813059


Related references

Fundamental properties of local anesthetics. II. Measured octanol:buffer partition coefficients and pKa values of clinically used drugs. Anesthesia and Analgesia 71(2): 158-170, 1990

Physicochemical properties/descriptors governing the solubility and partitioning of chemicals in water-solvent-gas systems. Part 1. Partitioning between octanol and air. Sar and Qsar in Environmental Research 17(3): 285-297, 2006

Enhancement of the 1-Octanol/Water Partition Coefficient of the Anti-Inflammatory Indomethacin in the Presence of Lidocaine and Other Local Anesthetics. Journal of Physical Chemistry. B 119(30): 9868-9873, 2015

PH dependence of the relative hydrophobicity and lipophilicity of amino acids and peptides measured by aqueous two-phase and octanol-buffer partitioning. Journal of Peptide Research 61(2): 71-79, 2003

Temperature dependence of the action of nerve blocking agents and its relationship to membrane buffer partition coefficients thermodynamic implications for the site of action of local anesthetics. British Journal of Pharmacology 81(1): 161-168, 1984

The temperature dependence and thermodynamics of partitioning of phenols in the n octanol water system. International Journal of Pharmaceutics 6(3-4): 339-348, 1980

The temperature dependence and thermodynamics of partitioning of phenols in the n-octanol-water system. International Journal of Pharmaceutics 6(3-4): 339-348, 1980

Interfacial ionization and partitioning of membrane-bound local anesthetics. Biochimica et Biophysica Acta 1103(1): 62-68, 1992

Temperature dependence and thermodynamics of partitioning of clofazimine analogues in the n-octanol/water system. International Journal of Pharmaceutics 58(2): 107-113, 1990

Temperature dependence and thermodynamics of partitioning of clofazimine analogues in the n octanol water system. International Journal of Pharmaceutics 58(2): 107-114, 1990

Relative hydrophobicity and lipophilicity of beta-blockers and related compounds as measured by aqueous two-phase partitioning, octanol-buffer partitioning, and HPLC. European Journal of Pharmaceutical Sciences 17(1-2): 81-93, 2002

Relative hydrophobicity and lipophilicity of drugs measured by aqueous two-phase partitioning, octanol-buffer partitioning and HPLC. A simple model for predicting blood-brain distribution. European Journal of Medicinal Chemistry 38(4): 391-396, 2003

Fundamental Properties of Local Anesthetics. Anesthesia & Analgesia 87(4): 885-889, 1998

Fundamental Properties of Local Anesthetics. Anesthesia & Analgesia 66(2): 159-165, 1986

Fundamental Properties of Local Anesthetics. Anesthesia & Analgesia 67(2): 159-165, 1987