An overview of the pharmacokinetics of cilomilast (Ariflo (R)), a new, orally active phosphodiesterase 4 inhibitor, in healthy young and elderly volunteers

The oral pharmacokinetics of cilomilast (Ariflo (R)) were investigated in f ive separate studies in healthy volunteers. Cilomilast was rapidly absorbed , and pharmacokinetics were dose proportional after single and repeat dosin g. The elimination half-life was 7 to 8 hours; accordingly, steady state wa s reached on the 3rd day of dosing. The degree of accumulation following re peat twice-daily dosing was predictable from the data following a single do se. Although systemic exposure (A UC) was, on average, 21% higher in elderl y (65-84 years) compared with young subjects, values for C-max and t(1/2) w ere similar, and no difference in tolerability was noted. Single and repeat doses of cilomilast up to and including 15 mg (dosed before or taken betwe en meals) were well tolerated. Dosing with food reduced the rate of absorpt ion without affecting total bioavailability. Hence, tolerability was optima l in the fed state; repeat doses up to and including 30 mg twice daily afte r meals were well tolerated following dose titration. (C) 2001 the American College of Clinical Pharmacology.