Pharmacokinetics and Bioavailability of Intranasal Fluticasone in Humans

McDowall, Jo E.; Mackie, Alison E.; Ventresca, G. P.; Bye, Alan

doi:10.2165/00044011-199714010-00006

Cited by 24 publications

(15 citation statements)

References 7 publications

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“…In the present study we did not investigate the relationship between dose and systemic exposure to FP, but based the dose regimen on a previous study [1], and estimated the minimum FPANS dose rate required to produce a detectable concentration with the assay used. However, in other studies C max and AUC values for intranasally administered triamcinolone acetonide [7] and BDP [8] were shown to be dose‐dependent.…”

Section: Discussionmentioning

confidence: 99%

“…Daily doses exceeding 2400 µg are well tolerated when given as a nasal spray [1, 2]. A new assay was developed using the technique of liquid chromatography tandem mass spectrometry (LC‐MS‐MS), which is more sensitive than the radioimmunoassay used previously (50 pg ml −1 ) [1, 3]. The assay used in the present study provides a lower limit of quantification of 20 pg ml −1 , sufficient to monitor systemic concentrations of inhaled FP at therapeutic doses [3].…”

Section: Introductionmentioning

confidence: 99%

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Systemic bioavailability of fluticasone propionate administered as nasal drops and aqueous nasal spray formulations

Daley‐Yates

Baker²

2001

Brit J Clinical Pharma

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Aims To measure and compare the systemic bioavailability of fluticasone propionate aqueous nasal spray and a new nasal drop formulation, using a sensitive analytical method and high dose regimen. Methods Volunteers received four 800 µg doses of fluticasone propionate as a nasal spray or drops over 2 days, separated by an 8 h dose interval. On day 2, blood samples were collected for assay of fluticasone propionate plasma concentrations. Results The mean systemic exposure, for both formulations was 8.5 pg ml−1 h (drops) and 67.5 pg ml−1 h (spray). Mean absolute bioavailabilities were estimated to be 0.06% (drops) and 0.51% (spray), by reference to historical intravenous data. Conclusions Both formulations exhibited low systemic bioavailability, even at 12 times the normal daily dose. The bioavailability from the nasal drops was approximately eight times lower than from the nasal spray.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Systemic bioavailability of fluticasone propionate administered as nasal drops and aqueous nasal spray formulations

Daley‐Yates

Baker²

2001

Brit J Clinical Pharma

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“…(<2%) [17] and suggested for MF (<0.1%) [18], might be related to a rapid mucociliary clearance from the nasal For the pMDI formulation, not only the extent of systemic absorption ( F ) of budesonide but also the plasma mucosa as both drugs, due to a higher lipophilicity, can be assumed to have a poor solubility compared to concentration profile, described by a lower C max , and a longer t max and MAT differed from that of the other two budesonide on the nasal mucosa. The low figures of systemic availability claimed for FP and MF may also be formulations.…”

mentioning

confidence: 99%

Systemic availability of budesonide after nasal administration of three different formulations: pressurized aerosol, aqueous pump spray, and powder

Thorsson

Borgå²,

Edsbäcker

1999

Brit J Clinical Pharma

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AimsThe present study was undertaken to determine the absolute systemic availability of budesonide from three different devices for nasal administration: pressurized aerosol, aqueous pump spray, and powder. Methods Sixteen healthy, non-smoking, volunteers participated in this open, randomized, and crossover study. All subjects received budesonide as an intravenous dose of 400 mg, and as three, single-dose, intranasal administrations: pressurized aerosol 800 mg, aqueous pump spray 400 mg, and powder 800 mg. Blood was sampled for 10 h after each administration and budesonide was assayed in plasma by liquid chromatography plus mass spectrometry. Results The mean [95% CI] systemic availability of budesonide with reference to the metered dose was: 13 [10; 15]%, 29 [23; 37]%, and 20 [16; 23]%, and the maximum plasma concentration (C max ) was attained at (t max ) 2.0, 0.7, and 0.4 h after administration for the pressurized aerosol, aqueous pump spray, and powder, respectively. Conclusions The uptake of budesonide was more rapid and more complete, and the systemic availability of the drug was significantly higher from the aqueous pump spray and powder than from the pressurized aerosol.

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“…The bioavailabilities of various inhaled corticosteroids have been reported in several studies, and show widely varying degrees of systemic exposure for these lipophilic drugs. 5-10 However, these studies generally do not specify initial regional deposition profiles of the nasal spray within the nose, which can differ between individual nasal geometries and administration methods (e.g. the nozzle insertion angle or the degree of patient inhalation).…”

Section: Introductionmentioning

confidence: 99%

Linking Suspension Nasal Spray Drug Deposition Patterns to Pharmacokinetic Profiles: A Proof-of-Concept Study Using Computational Fluid Dynamics

Rygg

Hindle

Longest

2016

Journal of Pharmaceutical Sciences

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The objective of this study is to link regional nasal spray deposition patterns of suspension formulations, predicted with computational fluid dynamics (CFD), to in vivo human pharmacokinetic (PK) plasma concentration profiles. This is accomplished through the use of CFD simulations coupled with compartmental PK modeling. Results showed a rapid initial rise in plasma concentration that is due to the absorption of drug particles deposited in the nasal middle passages, followed by a slower increase in plasma concentration that is governed by the transport of drug particles from the nasal vestibule to the middle passages. Although drug deposition locations in the nasal cavity had a significant effect on the shape of the concentration profile, the absolute bioavailability remained constant provided that all of the drug remained in the nose over the course of the simulation. Loss of drug through the nostrils even after long time periods resulted in a significant decrease in bioavailability and increased variability. The results of this study quantify how differences in nasal drug deposition affect transient plasma concentrations and overall bioavailability. These findings are potentially useful for establishing bioequivalence for nasal spray devices and reducing the burden of in vitro testing, pharmacodynamics and clinical studies.

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Pharmacokinetics and Bioavailability of Intranasal Fluticasone in Humans

Cited by 24 publications

References 7 publications

Systemic bioavailability of fluticasone propionate administered as nasal drops and aqueous nasal spray formulations

Systemic bioavailability of fluticasone propionate administered as nasal drops and aqueous nasal spray formulations

Systemic availability of budesonide after nasal administration of three different formulations: pressurized aerosol, aqueous pump spray, and powder

Linking Suspension Nasal Spray Drug Deposition Patterns to Pharmacokinetic Profiles: A Proof-of-Concept Study Using Computational Fluid Dynamics

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