Levofloxacin-Induced QTc Prolongation Depends on the Time of Drug Administration
| Autor: | L, Kervezee, V, Gotta, J, Stevens, W, Birkhoff, Imc, Kamerling, M, Danhof, J H, Meijer, J, Burggraaf |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Clinical Trials as Topic Cross-Over Studies Administration Oral Levofloxacin Middle Aged Drug Administration Schedule Circadian Rhythm Electrocardiography Long QT Syndrome Random Allocation Young Adult Heart Conduction System Humans Computer Simulation Letters to the Editor Letter to the Editor |
| Zdroj: | CPT: Pharmacometrics & Systems Pharmacology |
| ISSN: | 2163-8306 |
| Popis: | Understanding the factors influencing a drug's potential to prolong the QTc interval on an electrocardiogram is essential for the correct evaluation of its safety profile. To explore the effect of dosing time on drug-induced QTc prolongation, a randomized, crossover, clinical trial was conducted in which 12 healthy male subjects received levofloxacin at 02:00, 06:00, 10:00, 14:00, 18:00, and 22:00. Using a pharmacokinetic-pharmacodynamic (PK-PD) modeling approach to account for variations in PKs, heart rate, and daily variation in baseline QT, we find that the concentration-QT relationship shows a 24-hour sinusoidal rhythm. Simulations show that the extent of levofloxacin-induced QT prolongation depends on dosing time, with the largest effect at 14:00 (1.73 (95% prediction interval: 1.56-1.90) ms per mg/L) and the smallest effect at 06:00 (-0.04 (-0.19 to 0.12) ms per mg/L). These results suggest that a 24-hour variation in the concentration-QT relationship could be a potentially confounding factor in the assessment of drug-induced QTc prolongation. |
| Databáze: | OpenAIRE |
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