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F. Audren, P. Massin, M. Tod, R. Benosman, B. Haouchine, A. Erginay, C. Caulin, J.–F. Bergmann, A. Gaudric; A PHARMACOKINETIC–PHARMACODYNAMIC MODELING OF THE EFFECT OF TRIAMCINOLONE ACETONIDE ON CENTRAL MACULAR THICKNESS IN PATIENTS WITH DIABETIC MACULAR EDEMA . Invest. Ophthalmol. Vis. Sci. 2004;45(13):4100.
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Purpose:To develop a population model capable of describing the profile of the effect of intravitreal triamcinolone in the treatment of diabetic diffuse macular edema. Methods: The results of 56 injections in 39 eyes (34 patients), with diffuse diabetic macular edema were studied, using population pharmacokinetic–pharmacodynamic modeling, without concentration measurements. This approach was supported (1) by the pharmacokinetic hypothesis that the intravitreal concentration of triamcinolone decreases in accordance with an exponential biphasic equation and (2) by a pharmacodynamic hypothesis based on an indirect pharmacodynamic model. Central macular thickness (CMT), measured by optical coherence tomography (OCT) was chosen as the pharmacodynamic criterion. The covariates liable to affect the model were tested. Results: The pharmacodynamic profile of the effect of triamcinolone on CMT was characterized by a curve in 3 phases, comprising a fast decrease, a steady state, and a relapse. The confidence interval of most of the estimated parameters of the model was narrow. The mean estimated half–life of triamcinolone (±SD) was 15.4 ± 1.9 days and the mean maximum duration of its effect (± SD), 140 ± 17 days. Conclusions: The pharmacokinetic–pharmacodynamic modeling approach using CMT constitutes a valid alternative to pharmacokinetics studies. This approach worked excellently here, and our results are consistent with those published for the intraocular pharmacokinetics of TA in the human eye. We believe that this type of investigation is of interest as it avoids intraocular measurements whenever possible.
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