Tissue Distribution of Ciclesonide and Budesonide in Mice

Mårs, Ulla; Johansson, Alf; Evetovics, E.; Sjölin, Petter; Miller‐Larsson, Anna; Edsbäcker, Staffan

doi:10.1016/j.jaci.2005.12.758

Cited by 1 publication

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“…The higher tissue accumulation of des‐CIC may be related to its higher lipophilicity and greater protein binding . These results obtained after subcutaneous administration are consistent with an earlier intravenous study, where we showed that after 3 daily doses, des‐CIC accumulation was 3 times higher than that of BUD .…”

Section: Discussionsupporting

confidence: 91%

“…Subcutaneous administration also allowed reducing variability of administered doses and improving confidence in generated data. The relevance of subcutaneous administration route for systemic distribution was confirmed in a pilot study showing that des‐CIC and BUD were systemically distributed in a similar fashion after subcutaneous as after intravenous administration . To attain sufficient sensitivity in the autoradiographic and radiochromatographic analyses, the subcutaneous doses of des‐CIC and BUD applied in the present study were up to ten times higher than the highest inhaled daily dose in human beings and determined by the specific radioactivity of the compounds.…”

Section: Discussionmentioning

confidence: 55%

“…For BUD, only single‐dose whole‐body autoradiography data in mice have been published . In a preliminary evaluation, we have shown that des‐CIC accumulates in most tissues to a greater extent than BUD after 3 daily intravenous administrations .…”

mentioning

confidence: 94%

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Tissue Accumulation Kinetics of Ciclesonide‐active Metabolite and Budesonide in Mice

Mårs

d'Argy

Hallbeck

et al. 2013

Basic Clin Pharma Tox

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Inhaled corticosteroids (ICS) are mainstay treatment of asthma and chronic obstructive pulmonary disease. However, highly lipophilic ICS accumulate in systemic tissues, which may lead to adverse systemic effects. The accumulation of a new, highly lipophilic ICS, ciclesonide and its active metabolite (des-CIC) has not yet been reported. Here, we have compared tissue accumulation of des-CIC and an ICS of a moderate lipophilicity, budesonide (BUD), after 14 days of once-daily treatment in mice. Single, three or 14 daily doses of [ H]-des-CIC or [3 H]-BUD were administered subcutaneously to male CD1 albino mice, which were killed at 4 hr, 24 hr or 5 days after the last dose. Distribution of tissue concentration of radioactivity was studied by quantitative whole-body autoradiography. Pattern of radioactivity distribution across most tissues was similar for both corticosteroids after a single as well as after repeated dosing. However, tissue concentration of radioactivity differed between des-CIC and BUD. After a single dose, concentrations of radioactivity for both corticosteroids were low for most tissues but increased over 14 days of daily dosing. The tissue radioactivity of des-CIC at 24 hr and 5 days after the 14th dose was 2-3 times higher than that of BUD in majority of tissues. Tissue accumulation, assessed as concentration of tissue radioactivity 5 days after the 14th versus 3rd dose, showed an average ratio of 5.2 for des-CIC and 2.7 for BUD (p < 0.0001). In conclusion, des-CIC accumulated significantly more than BUD. Systemic accumulation may lead to increased risk of adverse systemic side effects during longterm therapy.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 55%