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- W2048625087 abstract "Ciclesonide, a novel glucocorticosteroid, through a rapid metabolism to desisobutyryl-ciclesonide (des-ciclesonide), provides an effective treatment option for asthma episodes by the inhaled route of administration. The availability of pharmacokinetic parameters (clearance [CL/F]; volume of distribution [Vd/F]; elimination half-life [T(½)]; and elimination rate constant [Kel]) in mice, rats, rabbits, and dogs enabled the prediction of human parameter values for des-ciclesonide using the well-accepted tool of allometry after intravenous administration of ciclesonide. However, as a result of the rapid conversion of ciclesonide, it was possible to perform allometry for the CL parameter only. Simple allometry (CL = 4.781W⁰·⁷⁸⁷⁴; R² = 0.9968) appeared to predict the CL of ciclesonide in close proximity of the observed value (observed: 101.25 L/h versus predicted: 135.62 L/h). In a similar manner, simple allometry predicted the human pharmacokinetic parameters of des-ciclesonide (CL/F, Vd/F, T(½), and Kel) within a two- to threefold range of the observed values. The allometric equations for des-ciclesonide parameter values were: CL/F = 4.8166W⁰·⁴⁹² (R² = 0.8598); Vd/F = 19.052W⁰·⁶³² (R² = 0.9049); T(½) = 3.7598W⁻⁰·¹⁶¹¹(R² = 0.8551); and Kel = 0.1832W⁰·¹⁵⁹⁶ (R² = 0.8632). In conclusion, the data suggested that allometry tool may be amenable for the prediction of the pharmacokinetic parameters of des-ciclesonide despite differences in the conversion rates and bioavailability of the active metabolite in various animal species." @default.
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- W2048625087 date "2013-05-01" @default.
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- W2048625087 title "Allometric Modeling of Ciclesonide, a Nonhalogenated Glucocorticoid, and Its Active Metabolite, Desisobutyrylciclesonide, Using Animal-Derived Pharmacokinetic Parameters" @default.
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- W2048625087 doi "https://doi.org/10.1097/mjt.0b013e31819df738" @default.
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