Safety, efficacy, and pharmacokinetic overview of low-dose daily administration of tadalafil.
BACKGROUND
Several phosphodiesterase type 5 (PDE5) inhibitors are commercially available for the treatment of erectile dysfunction (ED). Development of the first once-daily alternative dosing regimen with a PDE5 inhibitor was motivated by the behavioral complexities associated with sexual intimacy.


OBJECTIVE
To provide an alternative dosing option for certain men who may benefit from the removal of the temporal linkage between administration of an ED therapy and sexual intimacy or for men and their partners who anticipate at least twice-weekly sexual activity.


METHODS
Pharmacokinetic predictions of tadalafil plasma concentrations were generated based upon empirical data following 20-mg, single-dose administration coupled with tadalafil usage patterns from as-needed clinical trials. To support the pharmacokinetic simulations and pharmacodynamic assumptions, clinical trials were conducted to demonstrate the efficacy and safety of once-daily, low-dose tadalafil 2.5 and 5 mg.


METHODS
Simulated tadalafil plasma concentrations and comparison with safety and efficacy measures from clinical trials.


RESULTS
Based upon pharmacodynamic and pharmacokinetic data, once-daily doses of tadalafil 5 mg were predicted to provide therapeutic concentrations that would be maintained throughout the 24-hour dosing interval. Additionally, for a subgroup of men who anticipate at least twice-weekly sexual activity and are currently taking tadalafil 20 mg, a reduction in daily tadalafil exposure was predicted. To support the hypothesis that low-dose, once-daily tadalafil may be a safe and effective treatment alternative, clinical trials were conducted to demonstrate the safety and efficacy of once-daily tadalafil 2.5 and 5 mg. These results were similar to those of historical as-needed studies evaluating tadalafil 10 and 20 mg.


CONCLUSIONS
Consistent with pharmacokinetic predictions, data from clinical trials indicate that once-daily use of low-dose tadalafil is a safe and effective treatment for men with ED.
Wrishko
Rebecca
R
Eli Lilly and Company, Indianapolis, IN 46285, USA.
Sorsaburu
Sebastian
S
Wong
David
D
Strawbridge
Andrew
A
McGill
James
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D002243:Carbolines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004311:Double-Blind Method; D007172:Erectile Dysfunction / Q000188:drug therapy*; D006305:Health Status Indicators; D006801:Humans; D008297:Male; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000068581:Tadalafil; D013997:Time Factors
D002243:Carbolines; D010726:Phosphodiesterase Inhibitors; D000068581:Tadalafil