Low Systemic Bioavailability of Ciclesonide Aqueous Nasal Spray and Ciclesonide HFA Nasal Aerosol Compared With Orally Inhaled Ciclesonide

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RationaleThis study investigated the pharmacokinetics of 2 ciclesonide formulations for allergic rhinitis, an aqueous nasal spray and a hydro-fluoro-alkane (HFA) nasal aerosol, compared with a solution formulation of ciclesonide for treatment of asthma focusing on desisobutyryl-ciclesonide (des-CIC), the pharmacologically active metabolite of ciclesonide.MethodsHealthy volunteers (≥ 18 years; N = 30) were randomized in an open-label, single-dose, 3-period crossover study to 300 μg ciclesonide aqueous nasal spray, 300 μg ciclesonide HFA nasal aerosol (ciclesonide-HFA), or 320 μg ciclesonide orally inhaled by a metered-dose inhaler (MDI). Primary pharmacokinetic parameters are area under the serum concentration time curve extrapolated to infinity (AUCinf) and maximum serum concentraton (Cmax) of des-CIC. The safety and tolerability of ciclesonide were also evaluated.ResultsConcentrations of des-CIC above 10 pg/mL (= lower limit of quantification) were detected in only 3% of the serum samples in volunteers receiving ciclesonide aqueous. The highest value of des-CIC for this treatment was 26.7 pg/mL. Hence, bioavailability is too low to characterize pharmacokinetic properties accurately for this formulation. Mean Cmax (ng/L) of des-CIC for ciclesonide-HFA and orally inhaled ciclesonide were 59.1 and 586.2, respectively. Mean AUCinf of des-CIC for ciclesonide-HFA and for orally inhaled ciclesonide were 397.5 and 2,685 ng•h/L, respectively. The exposure of des-CIC following intranasal administration of HFA nasal is 14.3% compared to the inhalation using the same formulation via MDI.ConclusionsThe systemic bioavailability of des-CIC was low for both nasal ciclesonide formulations compared with orally inhaled ciclesonide with that of aqueous nasal spray lower than that of HFA nasal aerosol. RationaleThis study investigated the pharmacokinetics of 2 ciclesonide formulations for allergic rhinitis, an aqueous nasal spray and a hydro-fluoro-alkane (HFA) nasal aerosol, compared with a solution formulation of ciclesonide for treatment of asthma focusing on desisobutyryl-ciclesonide (des-CIC), the pharmacologically active metabolite of ciclesonide. This study investigated the pharmacokinetics of 2 ciclesonide formulations for allergic rhinitis, an aqueous nasal spray and a hydro-fluoro-alkane (HFA) nasal aerosol, compared with a solution formulation of ciclesonide for treatment of asthma focusing on desisobutyryl-ciclesonide (des-CIC), the pharmacologically active metabolite of ciclesonide. MethodsHealthy volunteers (≥ 18 years; N = 30) were randomized in an open-label, single-dose, 3-period crossover study to 300 μg ciclesonide aqueous nasal spray, 300 μg ciclesonide HFA nasal aerosol (ciclesonide-HFA), or 320 μg ciclesonide orally inhaled by a metered-dose inhaler (MDI). Primary pharmacokinetic parameters are area under the serum concentration time curve extrapolated to infinity (AUCinf) and maximum serum concentraton (Cmax) of des-CIC. The safety and tolerability of ciclesonide were also evaluated. Healthy volunteers (≥ 18 years; N = 30) were randomized in an open-label, single-dose, 3-period crossover study to 300 μg ciclesonide aqueous nasal spray, 300 μg ciclesonide HFA nasal aerosol (ciclesonide-HFA), or 320 μg ciclesonide orally inhaled by a metered-dose inhaler (MDI). Primary pharmacokinetic parameters are area under the serum concentration time curve extrapolated to infinity (AUCinf) and maximum serum concentraton (Cmax) of des-CIC. The safety and tolerability of ciclesonide were also evaluated. ResultsConcentrations of des-CIC above 10 pg/mL (= lower limit of quantification) were detected in only 3% of the serum samples in volunteers receiving ciclesonide aqueous. The highest value of des-CIC for this treatment was 26.7 pg/mL. Hence, bioavailability is too low to characterize pharmacokinetic properties accurately for this formulation. Mean Cmax (ng/L) of des-CIC for ciclesonide-HFA and orally inhaled ciclesonide were 59.1 and 586.2, respectively. Mean AUCinf of des-CIC for ciclesonide-HFA and for orally inhaled ciclesonide were 397.5 and 2,685 ng•h/L, respectively. The exposure of des-CIC following intranasal administration of HFA nasal is 14.3% compared to the inhalation using the same formulation via MDI. Concentrations of des-CIC above 10 pg/mL (= lower limit of quantification) were detected in only 3% of the serum samples in volunteers receiving ciclesonide aqueous. The highest value of des-CIC for this treatment was 26.7 pg/mL. Hence, bioavailability is too low to characterize pharmacokinetic properties accurately for this formulation. Mean Cmax (ng/L) of des-CIC for ciclesonide-HFA and orally inhaled ciclesonide were 59.1 and 586.2, respectively. Mean AUCinf of des-CIC for ciclesonide-HFA and for orally inhaled ciclesonide were 397.5 and 2,685 ng•h/L, respectively. The exposure of des-CIC following intranasal administration of HFA nasal is 14.3% compared to the inhalation using the same formulation via MDI. ConclusionsThe systemic bioavailability of des-CIC was low for both nasal ciclesonide formulations compared with orally inhaled ciclesonide with that of aqueous nasal spray lower than that of HFA nasal aerosol. The systemic bioavailability of des-CIC was low for both nasal ciclesonide formulations compared with orally inhaled ciclesonide with that of aqueous nasal spray lower than that of HFA nasal aerosol.