Blood pressure lowering effects of a new long-acting inhibitor of phosphodiesterase 5 in patients with mild to moderate hypertension.

Abstract

Inhibition of phosphodiesterase 5 is an attractive candidate mechanism for blood pressure (BP) lowering. In this study, a novel long-acting phosphodiesterase 5 inhibitor, PF-00489791, was evaluated in 133 patients with mild to moderate hypertension, randomized into 1 of 4 groups: placebo, 4 mg, 10 mg, and 20 mg titrated after 14 days of dosing to 40 mg. Study medication was administered once daily for 28 days. Ambulatory BP monitoring was used. There was a statistically significant decrease (compared with placebo) in mean daytime systolic BP on day 28 at the 10 and 20/40 mg doses (by approximately 5 and approximately 7 mm Hg, respectively). Changes in mean daytime diastolic BP corresponded with those in systolic BP. The magnitude of BP lowering was greater on day 1 than on days 14 and 28, but the response was sustained between days 14 and 28. PF-00489791 also exerted BP lowering effects on mean 24-hour ambulatory BP. There was a dose-related increase in plasma cGMP concentration (statistically significant at the 20/40 mg dose). There was an increased incidence of headaches at the 10 and 20/40 mg doses (22% and 21%, respectively, compared with 12% with placebo) and an increased incidence of dyspepsia/gastroesophageal reflux disease and musculoskeletal adverse events at the 20/40 mg dose. In conclusion, PF-00489791 causes a clinically meaningful and sustained BP lowering in patients with hypertension. It is generally safe and well tolerated at the clinically efficacious doses.

• Authors: Robert Wolk, William B Smith, Joel M Neutel, John Rubino, Dawei Xuan, James Mancuso, James Gilbert, Milton L Pressler
• Journal: Hypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 53 Issue 6 Pg. 1091-7 (Jun 2009) ISSN: 1524-4563 [Electronic] United States
• PMID: 19398651 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Humanized
• Antihypertensive Agents
• Delayed-Action Preparations
• Pharmaceutical Preparations
• Phosphodiesterase 5 Inhibitors
• ontamalimab
• Cyclic Nucleotide Phosphodiesterases, Type 5

Topics

• Administration, Oral
• Adolescent
• Adult
• Aged
• Antibodies, Monoclonal, Humanized
• Antihypertensive Agents (administration & dosage)
• Blood Pressure Monitoring, Ambulatory
• Cyclic Nucleotide Phosphodiesterases, Type 5 (administration & dosage)
• Delayed-Action Preparations (administration & dosage)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Administration Schedule
• Female
• Follow-Up Studies
• Humans
• Hypertension (diagnosis, drug therapy)
• Male
• Middle Aged
• Multivariate Analysis
• Pharmaceutical Preparations
• Phosphodiesterase 5 Inhibitors
• Reference Values
• Risk Assessment
• Severity of Illness Index
• Treatment Outcome
• Young Adult