Disposition Of Roflumilast In Pediatrics.

Roflumilast (ROF) is an oral PDE4 inhibitor in development for COPD and asthma. To date, the pharmacokinetics (PK) of ROF and its active N-oxide metabolite (RNO) have been characterized only in adults. Methods 13 children (c; 6–10y) and 12 adolescents (a; 11–16y) with mild asthma enrolled in an open, 2-period parallel study stratified by age. subjects received sequential single doses of 100 and 250μg. blood samples (14) were taken up to 72h. rof & rno were quantified by hplc/ms-ms and pk analyzed with standard methods. within- & between-group comparisons were made using 2-tailed, paired and unpaired t-tests. (see Table) Except for CMAX (100μg; p=0.01), PK parameters were not significantly different between A and C. Dose (μg/kg) and AUC∞ were linear (R2=0.34, P<0.01) for all subjects. A and C were not significantly different for mean elimination T½ of ROF (11.7 vs. 13.7h) and RNO (31.1 vs. 27.5h) or RNO formation ratio. Conclusions In patients 6–16y, PK of ROF appears not to vary as a function of age or dose over a 100 to 250μg range. Previous data showed similar disposition of ROF in older adolescents and adults. Clinical Pharmacology & Therapeutics (2005) 77, P29–P29; doi: 10.1016/j.clpt.2004.12.002 Rof 100μg Rof, 250μg Results (±sd) A C A C λz, 1/h 0.10 ± 0.004 0.13 ± 0.14 0.07 ± 0.05 0.10 ± 0.06 Tmax, h 0.79 ± 0.50 0.69 ± 0.32 0.75 ± 0.34 0.58 ± 0.19 Cmax, μg/l perμg/kg 1.13 ± 0.31 0.84 ± 0.20 1.05 ± 0.21 0.88 ± 0.25 Auc∞, μg/l*H perμg/kg 3.53 ± 0.69 3.74 ± 2.67 4.44 ± 2.02 3.91 ± 2.76 Vd/f, l/kg 3.06 ± 0.75 4.27 ± 2.05 4.73 ± 2.25 4.70 ± 2.66 Cl/f, l/h/kg 0.29 ± 0.006 0.38 ± 0.20 0.26 ± 0.10 0.37 ± 0.19