Platelet cyclic guanosine monophosphate as a biomarker of phosphodiesterase type 5 inhibitor efficacy in the treatment of erectile dysfunction: a randomized placebo-controlled study.

Abstract

BACKGROUND:

Phosphodiesterase 5 inhibitors (PDE5-Is) are a mainstay in the therapy of erectile dysfunction (ED). The primary end point of clinical efficacy, both in clinical studies and normal practice, is represented by the International Index of Erectile Function (IIEF).

OBJECTIVE:

To evaluate if platelet cyclic guanosine monophosphate (cGMP) could represent a valuable marker for PDE5-I activity in ED.

DESIGN, SETTING, AND PARTICIPANTS:

The study enrolled 46 patients with psychogenic, organic, and mixed ED (20-71 yr of age; IIEF score<26). Patients were randomized to 6 wk of vardenafil, 5 mg/d at bedtime, or placebo.

INTERVENTION:

All patients donated two blood samples, one before starting the protocol and the second after 6 wk of treatment.

MEASUREMENTS:

Platelet cGMP was measured in both placebo and vardenafil groups. All the patients completed the IIEF-Erectile Function (EF) domain and the sexual encounter profile (SEP) and underwent visual sexual stimulation (VSS) coupled with Rigiscan. All the measurements were performed prior to starting the protocol and after the 6 wk of treatment.

RESULTS AND LIMITATIONS:

Platelet cGMP production was significantly (p<0.05) elevated in patients taking 5mg vardenafil versus placebo. Vardenafil was not superior to placebo in improving IIEF-EF and SEP scores. Conversely, VSS-Rigiscan revealed a significant amelioration (p<0.028) in the vardenafil group versus placebo. The changes in platelet cGMP level correlated well with VSS-Rigiscan (p=0.0037) but not with IIEF-EF and SEP.

CONCLUSIONS:

Platelet cGMP could represent a relatively simple, reliable, and objective biomarker of PDE5-I activity in ED clinical studies. Larger clinical studies are needed to further validate the use, utility, and limits of this assay.

• Authors: Vincenzo Mirone, Roberta d'Emmanuele di Villa Bianca, Emma Mitidieri, Ciro Imbimbo, Ferdinando Fusco, Paolo Verze, Dino F Vitale, Raffaella Sorrentino, Giuseppe Cirino
• Journal: European urology (Eur Urol) Vol. 56 Issue 6 Pg. 1067-73 (Dec 2009) ISSN: 1873-7560 [Electronic] Switzerland
• PMID: 19781847 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Imidazoles
• Phosphodiesterase 5 Inhibitors
• Piperazines
• Placebos
• Sulfones
• Triazines
• Vardenafil Dihydrochloride
• Cyclic GMP-Dependent Protein Kinases
• Cyclic GMP

Topics

• Adult
• Aged
• Biomarkers (metabolism)
• Blood Platelets (metabolism)
• Cyclic GMP (metabolism)
• Cyclic GMP-Dependent Protein Kinases (metabolism)
• Dose-Response Relationship, Drug
• Drug Monitoring (methods, standards)
• Erectile Dysfunction (drug therapy)
• Humans
• Imidazoles (administration & dosage)
• Male
• Middle Aged
• Phosphodiesterase 5 Inhibitors (administration & dosage)
• Piperazines (administration & dosage)
• Placebos
• Reproducibility of Results
• Sulfones (administration & dosage)
• Triazines (administration & dosage)
• Vardenafil Dihydrochloride
• Young Adult