Single-dose study to compare the pharmacokinetics of HFA flunisolide and CFC flunisolide.
The hydrofluoroalkane (HFA) formulation of the inhaled corticosteroid flunisolide is a modification of the original chlorofluorocarbon (CFC) formulation. HFA flunisolide replaces CFC with an HFA propellant and uses a built-in spacer in its pressurized metered-dose inhaler. The average HFA flunisolide particle size is 1.2 microm compared with 3.8 microm for the CFC formulation. The smaller particle size improves lung targeting, allowing a reduction in the HFA flunisolide dose relative to CFC flunisolide while maintaining comparable efficacy. In a study of 12 healthy men, pharmacokinetic parameters were determined after single doses of 1000 microg CFC flunisolide delivered without a spacer, 340 microg HFA flunisolide delivered through a spacer, and 516 microg HFA flunisolide delivered without a spacer. A standard noncompartmental analysis of the concentration data was performed and mean (+/- S.D.) pharmacokinetic values were reported. Peak plasma concentrations (observed C(max)) were similar for the three treatments. Area under the curve up to the time corresponding to the last measurable concentration (AUC(0)(-)(tlast)) was similar for the CFC and HFA flunisolide, plus spacer groups (4.4 +/- 1.6 ng x h/mL and 5.0+/- 4.2 ng x h/mL, respectively); however, AUC(0)(-)(tlast) for the HFA flunisolide without spacer group was comparatively lower than for the CFC group (3.5 +/- 1.6 ng x h/mL). Observed C(max) and AUC(0)(-)(tlast) for 6 beta-OH flunisolide, the first-pass metabolite of flunisolide and an indicator of oropharyngeal deposition, were significantly higher in the CFC flunisolide group than in either HFA flunisolide group.
Nolting
Arno
A
Department of Pharmacokinetics, Forest Laboratories Incorporated, Harborside Financial Center, Plaza Three, Suite 602, Jersey City, New Jersey 07311, USA. arno.nolting@frx.com
Sista
Suryanarayana
S
Abramowitz
Wattanaporn
W
D000293:Adolescent; D000328:Adult; D000335:Aerosol Propellants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000704:Analysis of Variance; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D017402:Chlorofluorocarbons / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005446:Fluocinolone Acetonide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D009330:Nebulizers and Vaporizers / Q000706:statistics & numerical data; D005466:Fluorocarbons
D000335:Aerosol Propellants; D018927:Anti-Asthmatic Agents; D017402:Chlorofluorocarbons; D005446:Fluocinolone Acetonide; D006845:Hydrocarbons, Fluorinated; C007734:flunisolide; C094049:apaflurane; D005466:Fluorocarbons