QT prolongation

QA/QC Control Metrics QT Prolongation Quantification of Diug Effect Quantitative PCR Quinolinic Acid Quinolones... 

Kornick CA, Kilborn MJ, San tiago-Palma J, et al QTc interval prolongation associated with intravenous methadone. Pain 103 499-506, 2003 Krantz MJ, Lewkowiez L, Hays H, et al Torsade de pointes associated with very-high-dose methadone. Ann Intern Med 137 501-304, 2002 Krantz MJ, Kutinsky IB, Robertson AD, et al Dose-related effects of methadone on QT prolongation in a series of patients with torsade de pointes. Pharmacotherapy 23 802-805, 2003... 

Muzikant AL, Penland RC. Models for profiling the potential QT prolongation risk of drugs. Curr Opin Drug Discov Devel 2002 5 127-35. 

Moxifloxacin 400 mg once daily Not available rupture, photosensitivity, QT prolongation possible cost similar to amoxicillin/clavulanate... 

Chronic disease states or acute conditions that could be worsened by certain antimicrobial agents (e.g., QT prolongation or acute renal failure)... 

An additional guideline, ICHS7B, is in preparation which will address the assessment of potential for QT prolongation. In the meantime, CPMP 986/96 indicates the following preclinical studies should be conducted prior to first administration to humans ... 

Finally, a recent review [35] reported that QT prolongation (with or without TdP), together with hepatotoxicity, was responsible for more than 60% of drug withdrawals over the last 16 years. 

Cocaine is another example of a dmg with a complex pharmacological profile responsible for different properties probably concurring due to QT prolongation. It has a local anesthetic action (and therefore shares the pharmacological properties mentioned above), but recent reports also indicate the blockade of hERG K+ currents [47-49]. Thus, it is not unexpected that cocaine has been associated with QT prolongation and occurrence of TdP [50-53]. 

In conclusion, QT prolongation by hERG channel blockers is per se dose dependent, whereas actual occurrence of TdP depends on the repolarization reserve, which is variable among subjects and over time. The exception to the mle are those hERG blockers with multiple, sometimes complementary electrophysiological actions, which lead to a bell-shaped concentration-response curve [109]. 

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