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| Content Provider | Springer Nature Link |
|---|---|
| Author | Katagi, Jun Nakamura, Yuji Cao, Xin Ohara, Hiroshi Honda, Atsushi Izumi Nakaseko, Hiroko Ando, Kentaro Sugiyama, Atsushi |
| Copyright Year | 2015 |
| Abstract | In order to bridge the gap of action of dl-sotalol between the human ether-a-go-go-related gene (hERG) K$^{+}$ channel inhibition in vitro and QT-interval prolongation in vivo, its electropharmacological effect and pharmacokinetic property were simultaneously studied in comparison with those of 10 drugs having potential to prolong the QT interval (positive drugs: bepridil, haloperidol, dl-sotalol, terfenadine, thioridazine, moxifloxacin, pimozide, sparfloxacin, diphenhydramine, imipramine and ketoconazole) and four drugs lacking such property (negative drugs: enalapril, phenytoin, propranolol or verapamil) with the halothane-anesthetized guinea pig model. A dose of each drug that caused 10 % prolongation of Fridericia-corrected QT interval (QTcF) was calculated, which was compared with respective known hERG K$^{+}$ IC$_{50}$ value and currently obtained heart/plasma concentration ratio. Each positive drug prolonged the QTcF in a dose-related manner, whereas such effect was not observed by the negative drugs. Drugs with more potent hERG K$^{+}$ channel inhibition showed higher heart/plasma concentration ratio, resulting in more potent QTcF prolongation in vivo. The potency of dl-sotalol for QTcF prolongation was flat middle, although its hERG K$^{+}$ channel inhibitory property as well as heart/plasma concentration ratio was the smallest among the positive drugs, which may be partly explained by its lack of binding to plasma protein. |
| Starting Page | 138 |
| Ending Page | 146 |
| Page Count | 9 |
| File Format | |
| ISSN | 15307905 |
| Journal | Cardiovascular Toxicology |
| Volume Number | 16 |
| Issue Number | 2 |
| e-ISSN | 15590259 |
| Language | English |
| Publisher | Springer US |
| Publisher Date | 2015-03-31 |
| Publisher Place | New York |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | QT-interval prolongation Halothane Guinea pig Pharmacokinetics Pharmacodynamics Pharmacology/Toxicology Cardiology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Molecular Biology Toxicology Cardiology and Cardiovascular Medicine |
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