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

J Clin Pharmacol. 2001 Sep;41(9):950-8. doi: 10.1177/00912700122010924.

Abstract

The oral pharmacokinetics of cilomilast (Ariflo) were investigated in five separate studies in healthy volunteers. Cilomilast was rapidly absorbed, and pharmacokinetics were dose proportional after single and repeat dosing. The elimination half-life was 7 to 8 hours; accordingly, steady state was reached on the 3rd day of dosing. The degree of accumulation following repeat twice-daily dosing was predictable from the data following a single dose. Although systemic exposure (AUC) was, on average, 21% higher in elderly (65-84 years) compared with young subjects, values for Cmax and t(1/2) were similar, and no difference in tolerability was noted. Single and repeat doses of cilomilast up to and including 15 mg (dosed before or taken between meals) were well tolerated. Dosing with food reduced the rate of absorption without affecting total bioavailability. Hence, tolerability was optimal in the fed state; repeat doses up to and including 30 mg twice daily aftermeals were well tolerated following dose titration.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors*
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / metabolism
  • Area Under Curve
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / adverse effects
  • Bronchodilator Agents / pharmacokinetics*
  • Carboxylic Acids
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • Cyclohexanecarboxylic Acids
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Food-Drug Interactions
  • Humans
  • Male
  • Middle Aged
  • Nitriles
  • Phosphodiesterase Inhibitors / administration & dosage
  • Phosphodiesterase Inhibitors / adverse effects
  • Phosphodiesterase Inhibitors / pharmacokinetics*

Substances

  • Bronchodilator Agents
  • Carboxylic Acids
  • Cyclohexanecarboxylic Acids
  • Nitriles
  • Phosphodiesterase Inhibitors
  • Cilomilast
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 4