Pharmacokinetics of intravenous fluticasone propionate in healthy subjects

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 1000μg dose range.
2 The pharmacokinetics of FP can be regarded as being linear over this dosing range. FP was extensively distributed within the body ( V _ss 318  l), 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.