Population dose-response model for tadalafil in the treatment of male erectile dysfunction.
OBJECTIVE
To determine the population dose-response relationship for tadalafil during on-demand (as-needed) administration for treatment of erectile dysfunction (ED).


METHODS
A total of 212 male patients with mild, moderate, or severe ED participated in a multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Patients were randomized to receive placebo or 2, 5, 10, or 25 mg tadalafil, taken on demand over an 8-week period. Efficacy was assessed on the basis of questions 2 and 3 of the Sexual Encounter Profile (SEP) and questions 3 and 4 of the International Index of Erectile Function (IIEF) questionaires. These scores were modeled using logistic regression. A fifth patient response, the IIEF EF (erectile function) domain score, was modeled as a continuous variable.


RESULTS
The dose-response relationship for each efficacy variable was best described with an Emax model, in which maximum effect increased with ED severity at baseline. Response scores increased substantially between 10 and 25 mg tadalafil doses, and the dose-response parameter estimates suggested possibly higher responses at even higher doses.


CONCLUSIONS
Population dose-response modeling of all five oucome measures indicated that efficacy in all ED severity groups in the studied population generally increased across the 2 to 25 mg tadalafil dose range. Estimates of maximal improvement (Emax) in the IIEF EF domain score were 7.5, 11.4, and 16.3 points for patients with mild, moderate, and severe ED, respectively. Corresponding tadalafil doses to attain half-maximal improvement (ED50 estimates) were 4.7 mg, 7.1 mg, and 10.1 mg.
Staab
Alexander
A
Global Pharmacokinetics/Pharmacodynamics and Trial Simulation, Lilly Research Center, Windlesham, Surrey, United Kingdom.
Tillmann
Christiane
C
Forgue
S Thomas
ST
Mackie
Alison
A
Allerheiligen
Sandra R B
SR
Rapado
Javier
J
Trocóniz
Iñaki F
IF
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D002170:Canada / Q000453:epidemiology; D002243:Carbolines / Q000627:therapeutic use*; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D003710:Demography; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012646:Self Administration; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D000068581:Tadalafil
D002243:Carbolines; D004791:Enzyme Inhibitors; D000068581:Tadalafil; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human