title: Tadalafil population pharmacokinetics in patients with erectile dysfunction.
abstract: OBJECTIVE
  The purpose of this study was to characterize pharmacokinetics of tadalafil (Cialis) and potential sources of variability in patients with erectile dysfunction (ED).
  
  
  METHODS
  Population models were developed to describe tadalafil pharmacokinetics in 227 patients with mild to severe ED in a phase III trial. Parallel groups of patients received 2, 5, or 10 mg tadalafil or placebo orally, as needed, for 12 weeks.
  
  
  RESULTS
  Tadalafil pharmacokinetics in patients with ED were linear with respect to dose and duration of treatment, and a one-compartment model adequately described the data. The absorption rate was rapid (1.86 h(-1)), and the typical population estimates of the apparent oral clearance (CL/F) and apparent volume of distribution were 1.6 l/h and 63.8 l, respectively. Disposition parameters showed a moderate degree of interindividual variability (39-45%). The value of CL/F decreased slightly with increasing serum gamma-glutamyl transferase (GGT) concentration, the only statistically significant covariate detected. Systemic exposure to tadalafil was not influenced by age, weight, smoking status, alcohol consumption, liver enzyme status, ED severity, cardiovascular condition, or diabetes mellitus.
  
  
  CONCLUSIONS
  Pharmacokinetics in the efficacy/safety trial population are essentially similar to pharmacokinetics in healthy subjects, and no patient-specific factor warranting clinical consideration of dose regimen adjustment was identified in these analyses.
authors: Department of Pharmacy and Pharmaceutical Technology, University of Navarra, 31080, Pamplona, Spain.
authors: Iñaki F
authors: IF
authors: Trocóniz
authors: Christiane
authors: C
authors: Tillmann
authors: Alexander
authors: A
authors: Staab
authors: Javier
authors: J
authors: Rapado
authors: S Thomas
authors: ST
authors: Forgue
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000368:Aged; D019540:Area Under Curve; D002243:Carbolines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D018783:Impotence, Vasculogenic / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D000068581:Tadalafil; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D002243:Carbolines; D014665:Vasodilator Agents; D000068581:Tadalafil; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human