Document Detail

Accurate potentiometric determination of lipid membrane-water partition coefficients and apparent dissociation constants of ionizable drugs: electrostatic corrections.
MedLine Citation:
PMID:  19283456     Owner:  NLM     Status:  MEDLINE    
PURPOSE: Potentiometric lipid membrane-water partition coefficient studies neglect electrostatic interactions to date; this leads to incorrect results. We herein show how to account properly for such interactions in potentiometric data analysis. MATERIALS AND METHODS: We conducted potentiometric titration experiments to determine lipid membrane-water partition coefficients of four illustrative drugs, bupivacaine, diclofenac, ketoprofen and terbinafine. We then analyzed the results conventionally and with an improved analytical approach that considers Coulombic electrostatic interactions. RESULTS: The new analytical approach delivers robust partition coefficient values. In contrast, the conventional data analysis yields apparent partition coefficients of the ionized drug forms that depend on experimental conditions (mainly the lipid-drug ratio and the bulk ionic strength). This is due to changing electrostatic effects originating either from bound drug and/or lipid charges. A membrane comprising 10 mol-% mono-charged molecules in a 150 mM (monovalent) electrolyte solution yields results that differ by a factor of 4 from uncharged membranes results. CONCLUSION: Allowance for the Coulombic electrostatic interactions is a prerequisite for accurate and reliable determination of lipid membrane-water partition coefficients of ionizable drugs from potentiometric titration data. The same conclusion applies to all analytical methods involving drug binding to a surface.
Mustafa M A Elsayed; Ulrich Vierl; Gregor Cevc
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Publication Detail:
Type:  Journal Article     Date:  2009-03-13
Journal Detail:
Title:  Pharmaceutical research     Volume:  26     ISSN:  1573-904X     ISO Abbreviation:  Pharm. Res.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-05-06     Completed Date:  2009-08-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8406521     Medline TA:  Pharm Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1332-43     Citation Subset:  IM    
IDEA AG, Frankfurter Ring 193a, Munich, Germany.
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MeSH Terms
Bupivacaine / chemistry
Diclofenac / chemistry
Ions / chemistry
Ketoprofen / chemistry
Membrane Lipids / chemistry*
Naphthalenes / chemistry
Osmolar Concentration
Pharmaceutical Preparations / chemistry*
Potentiometry / methods*
Sensitivity and Specificity
Static Electricity
Water / chemistry*
Reg. No./Substance:
0/Ions; 0/Membrane Lipids; 0/Naphthalenes; 0/Pharmaceutical Preparations; 15307-86-5/Diclofenac; 2180-92-9/Bupivacaine; 22071-15-4/Ketoprofen; 7732-18-5/Water; 91161-71-6/terbinafine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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