丙酸氟替卡松
药代动力学
基于生理学的药代动力学模型
吸收(声学)
化学
吸入
消除速率常数
分布(数学)
氟替卡松
药理学
分配量
麻醉
医学
数学
材料科学
复合材料
数学分析
作者
Sriram Krishnaswami,Günther Hochhaus,H Möllmann,Jeffrey T. Barth,H Derendorf
出处
期刊:International Journal of Clinical Pharmacology and Therapeutics
[Dustri-Verlag Dr. Karl Feistle]
日期:2005-03-01
卷期号:43 (03): 117-122
被引量:17
摘要
Reports characterizing the pharmacokinetics of inhaled fluticasone propionate (FP) using compartmental approaches have suggested that the absorption of FP into the systemic circulation is rapid with a half-life of approximately 10 min. We believe that this is a classical case of misassignment of the pharmacokinetic parameter estimates, a problem often encountered while modeling pharmacokinetic data. The objective of this study was to illustrate and analyze this problem using actual blood level data of FP obtained in 14 healthy subjects.Serum concentration-time data of FP were obtained from a double-blind, randomized study involving single and multiple twice-daily inhalations of 500 microg via a dry powder device, Diskus. The profiles were fitted using one- and two-compartment pharmacokinetic models with first order absorption. Various permutations of the resulting exponential rate constants were analyzed to determine the combination that was most consistent with the underlying physical process.The two-compartment body model with first order absorption gave excellent fits for the observed FP concentrations after both single and multiple dosing. Even though peak levels were reached relatively early (30 - 90 min) after inhalation, the combination that most appropriately described the underlying process was alpha > Ka > beta, i.e. slow absorption, rapid distribution and slower elimination kinetics. The absorption, distribution and elimination half-lives resulted to be 3.8 h, 9.9 min and 13.6 h, respectively, consistent with the high lipophilicity and sustained dissolution characteristics observed in vitro.Analysis of FP pharmacokinetics after inhalation represents a classical case of potential misassignment of the exponential rate constants, which if ignored, could lead to erroneous interpretations regarding the underlying process. The study also elucidates the pitfall of using t(max) to calculate absorption rate.
科研通智能强力驱动
Strongly Powered by AbleSci AI