Modeling and simulation of sexual activity daily diary data of patients with female sexual arousal disorder treated with sildenafil citrate (Viagra).
OBJECTIVE
To develop a model to explore the dose-response of sildenafil citrate in patients with female sexual arousal disorder (FSAD) based on telephone sexual activity daily diary (TSADD) data obtained in double-blind, placebo controlled clinical studies.


METHODS
Data were available on 614 patients with FSAD. A parametric model (Weibull distribution) was developed to describe the probability density function of the time between sexual events. Orgasm satisfaction scores and overall sexual satisfaction scores were simultaneously modeled as ordered categorical variables. Simulations were performed to evaluate the expected clinical response in patients with FSAD.


RESULTS
The expected time between sexual events was approximately 3.5 days. Satisfaction scores increased with time to achieve a plateau after 3 to 4 weeks on treatment. The expected probability of satisfying orgasm (score of 3 and higher) ranged from 34.7% for placebo to 41.6% for 100 mg sildenafil citrate. Treatment effect (difference from placebo) was 6.9% for 100 mg sildenafil citrate, ranging from 0.6 to 24.7% for testosterone levels of 0.1 to 4.0 pg/ml. The treatment effect in postmenopausal women was larger than in premenopausal women.


CONCLUSIONS
A modeling and simulation framework to support drug development in FSAD was developed. Sildenafil citrate demonstrated a dose-dependent effect in patients with FSAD.
Claret
Laurent
L
Pharsight Corporation, Strategic Consulting Services, Mountain View, California, USA.
Cox
Eugene H
EH
McFadyen
Lynn
L
Pidgen
Alwyn
A
Johnson
Patrick J
PJ
Haughie
Scott
S
Boolell
Mitra
M
Bruno
Rene
R
D000328:Adult; D000465:Algorithms; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008875:Middle Aged; D008960:Models, Psychological; D015233:Models, Statistical; D009948:Orgasm / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use*; D017698:Postmenopause / Q000523:psychology; D011687:Purines; D012725:Sexual Behavior / Q000187:drug effects* / Q000523:psychology; D020018:Sexual Dysfunctions, Psychological / Q000188:drug therapy* / Q000523:psychology; D000068677:Sildenafil Citrate; D012984:Software; D013450:Sulfones; D013689:Telephone
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate