Parenteral delivery of HPβCD: effects on drug-HSA binding.

AAPS PharmSciTech
Sergey V KurkovDonna Madden

Abstract

It is thought that cyclodextrins, such as 2-hydroxypropyl-β-cyclodextrin (HPβCD), will at high concentration affect pharmacokinetics of drugs through competitive binding with plasma proteins. Albumin is the major component of plasma proteins responsible for plasma protein binding. The purpose of this study was to evaluate in vitro the competitive binding of drugs between human serum albumin (HSA) and HPβCD in isotonic pH 7.4 phosphate buffer saline solution (PBS) at ambient temperature. Eight model drugs were selected based on their physicochemical properties and ability to form complexes with HSA and HPβCD. The drug/HPβCD stability constants (K(1:1)) were determined by the phase-solubility method and HSA/HPβCD competitive binding determined by an equilibrium dialysis method. Protein binding of drugs that are both strongly protein bound and have high affinity to HPβCD (i.e., have high K(1:1) value) is most likely to be affected by parenterally administered HPβCD. However, this in vitro study indicates that even for those drugs single parenteral dose of HPβCD has to be as high as 70 g to have detectable effect on their protein binding. Weakly protein bound drugs and drugs with low affinity towards HPβCD are insensitive to the cy...Continue Reading

References

Feb 1, 1995·The Journal of Pharmacy and Pharmacology·M Katakam, A K Banga
May 1, 1997·Pharmaceutical Research·V J Stella, R A Rajewski
Dec 31, 1997·Journal of Pharmaceutical and Biomedical Analysis·L Deschamps-LabatB Bannwarth
Sep 20, 2001·Combinatorial Chemistry & High Throughput Screening·D M WilsonR A Rourick
Apr 7, 2004·Journal of Pharmaceutical Sciences·Thorsteinn LoftssonMarcus E Brewster
Aug 12, 2004·Chemical & Pharmaceutical Bulletin·Kaneto Uekama
Sep 7, 2004·Journal of Pharmaceutical Sciences·Michelle P McIntoshRoger A Rajewski
Jun 1, 2005·Journal of Pharmaceutical and Biomedical Analysis·Mats A L ErikssonLars B Nilsson
Aug 16, 2005·International Journal of Pharmaceutics·Thorsteinn LoftssonMár Másson
Nov 30, 2005·Journal of Pharmaceutical Sciences·Christine S PerryWilliam N Charman
May 3, 2006·Chemical & Pharmaceutical Bulletin·Annett MikolaschUlrike Lindequist
Sep 26, 2006·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·J FliegerM Tatarczak
Dec 2, 2006·International Journal of Pharmaceutics·Thorsteinn Loftsson, Dominique Duchêne
Jul 3, 2007·Advanced Drug Delivery Reviews·Marcus E Brewster, Thorsteinn Loftsson
Jan 17, 2008·Advanced Drug Delivery Reviews·Talia R BugginsGlyn Taylor
Mar 14, 2008·Toxicologic Pathology·Valentino J Stella, Quanren He
Mar 19, 2008·Molecular Pharmaceutics·Christopher J KochanskyKenneth R Korzekwa
Aug 1, 2008·Journal of Medicinal Chemistry·Muhammad AlimuddinRussell Dahl
Aug 12, 2009·Journal of Pharmaceutical Sciences·Phatsawee JansookThorsteinn Loftsson
Nov 19, 2009·Drug Design, Development and Therapy·Mark WelliverRobert Redfern

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Citations

Oct 4, 2012·Journal of Pharmaceutical Sciences·Sergey V KurkovThorsteinn Loftsson
Jul 10, 2012·International Journal of Pharmaceutics·Sergey V Kurkov, Thorsteinn Loftsson
Jan 13, 2016·Biological & Pharmaceutical Bulletin·Ayumu AsaiHirokazu Okamoto
Jan 18, 2011·International Journal of Pharmaceutics·Martin MessnerThorsteinn Loftsson
Feb 27, 2015·Pharmaceutical Development and Technology·Milica Vukićević, Hanne Hjorth Tønnesen
Jun 11, 2015·The Journal of Pharmacy and Pharmacology·Thorsteinn LoftssonAngel Concheiro
Jul 29, 2016·Pharmaceutical Development and Technology·Victoria J Valerón Bergh, Hanne Hjorth Tønnesen
Sep 7, 2018·Drug Development Research·Shery Jacob, Anroop B Nair
Oct 13, 2017·Basic & Clinical Pharmacology & Toxicology·Chutimon Muankaew, Thorsteinn Loftsson
Oct 19, 2020·Journal of Pharmaceutical Sciences·Thorsteinn Loftsson
May 6, 2021·Macromolecular Bioscience·Matin RostamitabarSamaneh Ghazanfari

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