Table 3.
Formation of des-CIC fatty acid esters in airway epithelial cells and lung tissue
| Test system | Substrate concentration (mol/L) | Substrate incubation time (h) | Sample collection time (h) |
Mean (SD) intracellular concentrationa |
|||
|---|---|---|---|---|---|---|---|
| CIC | Des-CIC | Des-CIC-oleate | Des-CIC-palmitate | ||||
| HNEC | 1 × 10−7 | 1 h | 24 hb | 0.31 (0.07) | 5.39 (0.99) | 48.43 (7.46) | 1.87 (0.34) |
| NHBE cells | 1 × 10−6 | 1 h | 24 hb | 5.22 (2.53) | 20.05 (1.55) | 14.10 (1.38) | 0.59 (0.19) |
| A549 cells | 2 × 10−8 | 1 h | 24 hb | 2.31(0.55) | 3.19 (0.38) | 23.20(6.03) | 0.74 (0.15) |
| Lung slices | 1 × 10−5 | 24 h | 24 h | 2.93 (0.46) | 3.23 (0.42) | 3.46 (2.29) | |
a
Amount of ciclesonide and metabolite in HNEC (pmol/dish), NHBE (pmol/well), A549 (pmol/dish), lung tissue (nmol).
b
Incubation in substrate-free medium.
Abbreviations: HNEC, human bronchial epithelial cells; NHBE, normal human bronchial epithelial; des-CIC, desisobutyryl-ciclesonide. (Derived from data of Nave et al 2007; Nonaka et al 2007; Sato et al 2007a; Nonaka unpublished data).