Moxifloxacin versus placebo modeling of the QT interval.

Journal of Pharmacokinetics and Pharmacodynamics
Philippe Grosjean, Saïk Urien

Abstract

The objectives were to develop a population model for placebo-corrected moxifloxacin QT interval in healthy subjects using non-linear mixed effects modeling and to examine effect of covariates on the observed QT. Based on the parameters of interest, optimizations of observation times and number of subjects were proposed. A pool of four thorough QT studies was used, representing 99 subjects receiving placebo and moxifloxacin. The data was modeled using Monolix. The placebo effect on QT was satisfactorily described using a 2-oscillator model. It reflected the circadian rhythm variability which is taken into account when assessing the time-matched mean difference on QT between treatment and baseline. Based on this model, the moxifloxacin effect on QT was satisfactorily described by the same equation with the adjunct of a direct and proportional drug concentration-effect. The Emax model provided the best description of the effect. The unique covariate was gender for both baseline QTc and individual heart rate correction factor. The present design included up to 16 observations for pharmacodynamics. Using this model, 9 observation times for pharmacodynamics provided satisfactory estimates for the parameters of interest (Emax). With ...Continue Reading

References

Jul 1, 1983·The American Journal of Cardiology·K F BrowneD P Zipes
Jun 26, 1999·The Journal of Antimicrobial Chemotherapy·H Stass, D Kubitza
May 16, 2001·Clinical Pharmacokinetics·J T SullivanA H Heller
Apr 12, 2003·Pacing and Clinical Electrophysiology : PACE·Peter SmetanaMarek Malik
Jul 27, 2007·Journal of Pharmacokinetics and Pharmacodynamics·Radojka M SavicMats O Karlsson
Dec 21, 2007·Journal of Clinical Pharmacology·Daniel Bloomfield, Rajesh Krishna
Dec 21, 2007·Journal of Clinical Pharmacology·Tanya RussellRichard L Lalonde
Dec 21, 2007·Journal of Clinical Pharmacology·Christine E GarnettJogarao V Gobburu
Sep 2, 2008·Journal of Clinical Pharmacology·Marek MalikDavid Madge
Oct 22, 2008·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Marek MalikPeter Smetana
Oct 23, 2008·Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences·J R FernándezA Mojón
Feb 25, 2009·Clinical Pharmacology and Therapeutics·D M BloomfieldJ A Wagner
Nov 7, 2009·Computer Methods and Programs in Biomedicine·Caroline BazzoliFrance Mentré
Mar 19, 2011·Journal of Clinical Pharmacology·Philippe Grosjean, Saïk Urien
Jan 1, 2009·Language Learning and Development : the Official Journal of the Society for Language Development·Daniel J WeissAaron D Mitchel

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Citations

Nov 11, 2015·Pharmaceutical Research·V F S DuboisUNKNOWN TI Pharma PKPD Platform
Jun 19, 2014·British Journal of Clinical Pharmacology·Nicholas P France, Oscar Della Pasqua
Aug 6, 2016·Pharmaceutical Statistics·Bernard SébastienJérôme Msihid
Jul 25, 2018·Journal of Clinical Pharmacology·Jörg TäubelA John Camm
Nov 22, 2019·CPT: Pharmacometrics & Systems Pharmacology·Yeamin HuhTimothy Nicholas
Apr 20, 2017·Journal of Pharmacokinetics and Pharmacodynamics·Peter L Bonate
Mar 1, 2014·Therapeutic Innovation & Regulatory Science·David Hoffman

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