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  • Title: [Quantitative interpretation of dexamethasone pharmacokinetics in human inner ear perilymph using computer simulations].
    Author: Liu H, Dong M.
    Journal: Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi; 2010 Nov; 24(22):1040-3. PubMed ID: 21322932.
    Abstract:
    OBJECTIVE: To study the dexamethasone pharmacokinetics of human inner ear perilymph under different drug administration using computer simulations. METHOD: The dexamethasone pharmacokinetics in guinea pigs inner ear perilymph under an intratympanic application with high-performance liquid chromatography. Dexamethasone pharmacokinetics in the guinea pigs cochlear fluid were simulated with a computer model, the Washington University Cochlear Fluids Simulator, version 1.6 and the best Simulations parameters to the experimental data could be obtain. With best Simulations parameters based on the experimental data, seven kinds application protocols were designed for human inner ear perilymph. RESULT: After an intratympanic application dose of 0.5% dexamethasone 150 ml in guinea pigs, the T(1/2K) was (2.918 +/- 0.089) h, and Cmax was (231.25 +/- 6.89) microg/L. The best Simulations parameters were that concentration of the dexamethasone 21-Phosphate disodium salt was 0.5% and the formula weight was 516, as well as drug diffusion coefficient was 0.6939 x 10(-5) cm2/s and round window permeability was 2.2 x 10(-11) cm/s while drug clearance half time was 175 minutes and scala tympaniscala vestibuli communication was 45 minutes. After an intratympanic application dose of 0.5% dexamethasone 500 mL, which the applied drug stayed in contact with the round window membrane for 15, 30, 60 and 120 minutes, the Cmax was 32.8, 64.3, 122.6 and 203.3 microg/L and the AUC was 116.5, 229.1, 423.6 and 759.2 microg/(h x L), respectively. After an intratympanic application dose of 0.5%, 1%, 2% and 4% dexamethasone 500 ml, which the applied drug stayed in contact with the round window membrane for 30 minutes respectively, the Cmax was 64.3, 127.3, 255.4 and 575.6 microg/L respectively and the AUC was 229.1, 462.8, 920.59 and 1525.2 microg/(h x L), respectively. CONCLUSION: The dexamethasone pharmacokinetics in human inner ear perilymph by computer simulations was reported. As the time contact with the round window membrane increased, the inner ear perilymph concentration of dexamethasone increased. As the concentration of dexamethasone increased, the inner ear perilymph concentration of drug increased.
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