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.

Conclusion: 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.