Evidence map›Paper›PMID 19283456›Full record

ArticlePharmaceutical research2009

Accurate potentiometric determination of lipid membrane-water partition coefficients and apparent dissociation constants of ionizable drugs: electrostatic corrections.

Mustafa M A Elsayed, Ulrich Vierl, Gregor Cevc

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Article in Pharmaceutical research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.8field-weighted citation impact, top 30% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 19 citations in OpenAlex.

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4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 1 country.

Mustafa M A ElsayedIDEA AG, Frankfurter Ring 193a, Munich, Germany. mmaelsayed@gmail.com
Ulrich Vierl
Gregor Cevc
IDEA (Germany) · DEIndividual Development and Adaptive Education · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposePotentiometric 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

methodsWe 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.

resultsThe 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.

conclusionAllowance 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.

Indexed as

BupivacaineDiclofenacIonsKetoprofenMembrane LipidsNaphthalenesOsmolar ConcentrationPharmaceutical PreparationsPotentiometrySensitivity and SpecificitySolubilityStatic ElectricityTerbinafineTitrimetryWaterBupivacaineDiclofenacIonsKetoprofenMembrane LipidsNaphthalenesPharmaceutical PreparationsTerbinafineWater

Identifiers

PMID19283456
OpenAlexW2002162180

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.