Tadalafil population pharmacokinetics in patients with erectile dysfunction.
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.
Trocóniz
Iñaki F
IF
Department of Pharmacy and Pharmaceutical Technology, University of Navarra, 31080, Pamplona, Spain.
Tillmann
Christiane
C
Staab
Alexander
A
Rapado
Javier
J
Forgue
S Thomas
ST
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
D002243:Carbolines; D014665:Vasodilator Agents; D000068581:Tadalafil; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human