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健康受试者中静脉注射丙酸氟替卡松的药代动力学

Pharmacokinetics of intravenous fluticasone propionate in healthy subjects.

作者信息

Mackie A E, Ventresca G P, Fuller R W, Bye A

机构信息

Clinical Pharmacology Division, GlaxoWellcome Research and Development, Greenford, Middlesex, UK

出版信息

Br J Clin Pharmacol. 1996 Jun;41(6):539-42. doi: 10.1046/j.1365-2125.1996.36110.x.

DOI:10.1046/j.1365-2125.1996.36110.x
PMID:8799519
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2042625/
Abstract
  1. Fluticasone propionate (FP) is a potent glucocorticoid used in the treatment of asthma. Prior to reporting the pharmacokinetics following the inhaled and oral routes, the pharmacokinetics need to be established following intravenous dosing. The present study determines the intravenous pharmacokinetics of FP, using non-compartmental analysis, in healthy male subjects over the 250 to 1000 micrograms dose range. 2. The pharmacokinetics of FP can be regarded as being linear over this dosing range. FP was extensively distributed within the body (Vss 3181), rapidly cleared (CL 1.1 l min-1) with a terminal elimination half-life of 7.8 h and a mean residence time of 4.9 h. 3. In order that future pharmacokinetic/pharmacodynamic and other modelling can be carried out, the plasma concentration-time profiles were parameterized using a model based on sums of exponentials, the appropriateness of this model was justified as the secondary kinetic parameters from the model were similar to those obtained using non-compartmental analysis.
摘要
  1. 丙酸氟替卡松(FP)是一种用于治疗哮喘的强效糖皮质激素。在报告吸入和口服途径后的药代动力学之前,需要先确定静脉给药后的药代动力学。本研究采用非房室分析方法,在250至1000微克剂量范围内,测定健康男性受试者中FP的静脉药代动力学。2. 在该给药范围内,FP的药代动力学可视为呈线性。FP在体内广泛分布(稳态分布容积Vss为3181),清除迅速(清除率CL为1.1升/分钟),终末消除半衰期为7.8小时,平均驻留时间为4.9小时。3. 为了能够进行未来的药代动力学/药效学及其他建模,使用基于指数和的模型对血浆浓度-时间曲线进行参数化,该模型的适用性得到了验证,因为该模型的二级动力学参数与使用非房室分析获得的参数相似。