Comparison of the Oropharyngeal Deposition of Inhaled Ciclesonide and Fluticasone Propionate in Patients With Asthma

Abstract

Ciclesonide is a novel inhaled corticosteroid that is converted in the lungs to its active metabolite, desisobutyryl-ciclesonide (des-CIC). The aim of this study was to compare the deposition of ciclesonide, as well as its conversion to des-CIC, in the oropharyngeal cavity with fluticasone propionate (FP) following inhalation via hydrofluoroalkane-propelled metered-dose inhalers (HFA-MDIs). Eighteen asthmatics inhaled ciclesonide 800 microg followed by FP 1000 microg or vice versa in an open, randomized, 2-treatment, 2-sequence study design. The oropharynx was washed out immediately and at 15, 30, 45, and 60 minutes after inhalation. Samples were analyzed for ciclesonide, des-CIC, and FP using liquid chromatography with tandem mass-spectrometric detection. Concentration-time curves and area under the concentration-time curve (AUC) were calculated for each drug. Ciclesonide and FP were recovered in almost all samples. Within 60 minutes after inhalation, the amounts of both ciclesonide and FP decreased sharply, and low residual levels were detected after 30 minutes. des-CIC was detected in relatively low concentrations, with maximum concentration 30 minutes following inhalation. The AUC(0-60 min) for ciclesonide (250.4 nmol x h/L) and des-CIC (37.8 nmol x h/L) were found to be significantly lower compared with FP (636.2 nmol.h/L, P < .001). Approximately 50% less ciclesonide and 90% less metabolite were present in the oropharynx compared with FP. Less than 20% of the residual ciclesonide in the oropharynx was metabolized to des-CIC. These findings indicate that oropharyngeal deposition of ciclesonide is only half that of FP following inhalation from an HFA-MDI. Furthermore, there is little activation of ciclesonide to its active metabolite in the oropharynx, suggesting a decreased likelihood of inhaled ciclesonide-associated oropharyngeal side effects.

Relevance of pharmacokinetics and pharmacodynamics of inhaled corticosteroids to asthma

“…Furthermore, the concentration of des-CIC in the oropharynx was 25-fold lower than that of BUD [44]. In a similar study comparing ciclesonide (800 mg ex-valve) and FP (1,000 mg) in patients with asthma, the oropharyngeal deposition of ciclesonide and des-CIC together was approximately half that of FP, and the deposition of des-CIC was only 8% of that of FP [45]. This lower oropharyngeal deposition and minimal activation to des-CIC leads to a reduced occurrence of local side-effects (e.g.…”

“…Ciclesonide has a much lower RRA (12) than des-CIC (1,200), and is, therefore, virtually pharmacologically inactive [24]. Studies have indicated that bioactivation of ciclesonide within the oropharynx is very low, resulting in lower amounts of active drug in the oropharyngeal region compared with BUD and FP [44,45].…”

Preclinical Profile of Ciclesonide, a Novel Corticosteroid for the Treatment of Asthma

“…des-CIC, which has high local antiinflammatory activity in the lung, is conjugated to fatty acids to prolong anti-inflammatory activity in the lung, is essentially devoid of oral bioavailability, has high protein binding in the systemic circulation, and is rapidly and completely eliminated from the body (Dietzel et al, 2001). Recent data suggest that the oropharyngeal deposition of ciclesonide is only half that of fluticasone with little activation to des-CIC following inhalation from a hydrofluoro-alkane-propelled metered-dose inhaler in asthmatics, suggesting a decreased likelihood of ciclesonide-associated side effects (Richter et al, 2005).…”

Ciclesonide in persistent asthma: the evidence of its therapeutic value

“…In a study of adults with bronchial asthma, the oropharyngeal deposition of ciclesonide was about 50% of that reported with fluticasone propionate, with 90% less des-CIC present in the oropharyngeal cavity compared with fluticasone following inhalation (Richter et al 2005). Following administration of ciclesonide and budesonide to healthy volunteers, the maximal concentrations of ciclesonide and des-CIC recovered from oropharyngeal wash were 30% and 0.67% of budesonide, respectively (Nave et al 2005a).…”