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《Journal of Clinical Otorhinolaryngology》 2005-22
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Methylprednisolone pharmacokinetics in perilymph and plasma of guinea pig after topical administration and intracardial injection

ZHANG Ping~1 WU Hao~1 YANG Jun~1 HOU Dongming~1 ZHANG Shunguo~2 CHEN Jie~1(~1Department of Otorhinolaryngology and Head-neck Surgery,Xinhua Hospital,Shanghai Second Medical University,Shanghai,200092,China;~2Department of Clinical Pharmacology,Xinhua Hospital affiliated Shanghai Second Medical University)  
Objective:To determine pharmacokinetics profiles of methylprednisolone(MTH) in perilymph and plasma of guinea pig after topical and systemic administration.Method:A granule gelfoam soaked with MTH((40 mg/ml)) was placed in the niche of round window of guinea pig;otocyst was infused with MTH(40 mg/ml);4 mg/kg of MTH was injected intracardially.Samples of blood and perilymph of the scala tympani were obtained 1~6 h after administration of two routes,respectively.High-performance liquid chromatography was used to assay MTH in the samples.Result:After intracardial injection of MTH,concentrations of drug in plasma were obviously higher than those of in perilymph in every hour while drug in perilymph could not be obtainted in 4~6 h,and the results were significantly different.After niche was placed with granule gelfoam with drug or otocyst was infused with MTH,drug could not be obtained in plasma,concentrations of drug in perilymph were obviously higher than those of in plasma after intracardial injection,and the highest concentrations in perilymph were manifested in 1 h(20 min).The concentrations of drug in perilimph after otocyst was infused with MTH were higher than those of after niche was placed with granule gelfoam soaked with MTH in every hour,and there were significant differences in between except those in 4 and 6 h.The half-life time of MTH in perilymph after otocyst was infused was 1.51 h,and the one after niche was placed with granule gelfoam soaked with MTH was 1.55 h.Conclusion:MTH could penetrate effectively through membrane of round window into the cochlear fluid and reach a much higher concentration following topical administration as compared with systemic application.The concentrations of drug in perilimph after otocyst was infused with MTH were higher.
【Fund】: 上海市科委基金资助项目(No:034119819)
【CateGory Index】: R96
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