Hydroxypropyl β-cyclodextrins: A misleading vehicle for the in vitro hERG current assay

Journal of Cardiovascular Pharmacology

Volumn 49, Issue 5, 2007, Pages 269-274

  Mikhail, Ann ^a   Fischer, Cristina ^a   Patel, Ameesha ^a   Long, Michelle A ^a   Limberis, James T ^a   Martin, Ruth L ^a   Cox, Bryan F ^a   Gintant, Gary A ^a   Su, Zhi ^a  

^a ABBOTT LABORATORIES   (United States)

Author keywords

Cisapride; E 4031; hERG; Hydroxypropyl cyclodextrins; Long QT; Terfenadine

Indexed keywords

1 [2 (6 METHYL 2 PYRIDYL)ETHYL] 4 (4 METHYLSULFONYLAMINOBENZOYL)PIPERIDINE; 2 HYDROXYPROPYL BETA CYCLODEXTRIN; CISAPRIDE; POTASSIUM CHANNEL HERG; TERFENADINE;

ARTICLE; CELL STRAIN HEK293; COMPLEX FORMATION; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG EFFECT; DRUG POTENCY; DRUG SOLUBILITY; EMBRYO; HUMAN; HUMAN CELL; IC 50; IN VITRO STUDY; PRIORITY JOURNAL; PROTEIN STRUCTURE; SCREENING; SENSITIVITY ANALYSIS; VOLTAGE CLAMP; WHOLE CELL;

ANTI-ARRHYTHMIA AGENTS; ARRHYTHMIA; BETA-CYCLODEXTRINS; BIOLOGICAL ASSAY; CISAPRIDE; DOSE-RESPONSE RELATIONSHIP, DRUG; ELECTROPHYSIOLOGY; ETHER-A-GO-GO POTASSIUM CHANNELS; EXCIPIENTS; GASTROINTESTINAL AGENTS; HISTAMINE H1 ANTAGONISTS; HUMANS; INHIBITORY CONCENTRATION 50; MYOCYTES, CARDIAC; PIPERIDINES; POTASSIUM CHANNEL BLOCKERS; PYRIDINES; SOLUBILITY; TERFENADINE; TIME FACTORS;

EID: 34249822208     PISSN: 01602446     EISSN: None     Source Type: Journal    
DOI: 10.1097/FJC.0b013e318036dd05     Document Type: Article

References (20)

1. Cavero I, Mestre M, Guillon JM, et al. Drugs that prolong QT interval as an unwanted effect: assessing their likelihood of inducing hazardous cardiac dysarrhythmias. Exp Opin Pharmacother. 2000;1:947-973.
2. DePonti F, Poluzzi E, Cavalli A, et al. Safety of non-antiarrhythmic drugs that prolong the QT interval or induce Torsade de Pointes. Drug Safety. 2002;25:263-286.
3. Martin RL, McDermott JS, Salmen HJ, et al. The utility of hERG and repolarization assays in evaluating delayed cardiac repolarization: influence of multi-channel block. J Cardiovasc Pharmacol. 2004;43:369-379.
4. Gintant GA, Su Z, Martin RL, et al. Utility of hERG assays as surrogate markers of delayed cardiac repolarization and QT safety. Toxocol Pathol. 2006;34:81-90.
5. Loftsson T, Brewster M. Pharmaceutical applications of cyclodextrins. 1. Drug solubilization and stabilization. J Pharm Sci. 1996;85:1017-1025.
6. Connors K. The stability of cyclodextrin complexes in solution. Chem Rev. 1997;97:1325-1357.
7. Challa R, Ahuja A, Ali J, et al. Cyclodextrins in drug delivery: an updated review. AAPS Pharm Sci Tech. 2005;6:E329-E357.
8. Zhou Z, Gong Q, Ye B, et al. Properties of HERG channels stable expressed in HEK-293 cells studies at physiological temperature. Biophys J. 1998;74:230-241.
9. Pan L, Ho Q, Tsutsui K, et al. Comparison of chromatographic and spectroscopic methods used to rank compounds for aqueous solubility. J Pharm Sci. 2001;90:521-529.
10. Loftsson T, Hreinsdóttir D, Másson M. Evaluation of cyclodextrin solubilization of drugs. Intl J Pharm. 2005a;302:18-28.
11. Al Omari MM, Zughul MB, Davies JED, et al. Factors contributing to solubility synergism of some basic drugs with β-cyclodextrin in ternary molecular complexes. J Inclusion Phenomena Macrocyclic Chem. 2006 epublication.
12. Loftsson T, Pekka J, Masson M, et al. Cyclodextrins in drug delivery. Exp Opin Drug Deliv. 2005b;2:335-351.
13. Junquera E, Aicart E. Thermodynamic analysis of the binding of a hepatoprotectant drug, thioctic acid, by β-cyclodextrin. J Pharm Sci. 1999;88:626-631.
14. Surapaneni S, Khalil SKW. Resolution of terfenadine enantiomers by reversed phase-high performance liquid chromatography using β-cyclodextrin as mobile phase additive. J Pharm Biomed Anal. 1996;14:1631-1634.
15. Choi H, Lee B, Han J, et al. Terfenadine-β-cyclodextrin Inclusion complex with antihistaminic activity enhancement. Drug Dev Ind Pharm. 2001;27:857-862.
16. Tong WQ, Lach J, Chin TF, et al. Microcalorimetric investigation of the complexation between 2-hydroxypropyl-β-cyclodextrin and amine drugs with the diphenylmethyl functionality. J Pharm Biomed Anal. 1991;9:1139-1146.
17. Christian AE, Haynes MP, Phillips MC, et al. Use of cyclodextrins for manipulating cellular cholesterol content. J Lipid Res. 1997;38:2264-2272.
18. Pouvreau S, Berthier C, Blaineau S, et al. Membrane cholesterol modulates dihydropyridine receptor function in mice fetal skeletal muscle cells. J Physiol. 2004;555:365-381.
19. Lam RS, Shaw AR, Duszyk M. Membrane cholesterol content modulates activation of BK channels in colonic epithelia. Biochim Biophys Acta. 2004;1667:241-248.
20. O'Connell KM, Tamkun MM. Targeting of voltage-gated potassium channel isoforms to distinct cell surface microdomains. J Cell Sci. 2005;118:2155-2166.