Pepducin PZ-128 Inhibits Platelet Protease-Activated Receptor-1

Rapid, specific, dose-dependent, reversible inhibition seen in patients with coronary artery disease

blood cells

FRIDAY, Dec. 18, 2015 (HealthDay News) -- The pepducin PZ-128 offers rapid, specific, dose-dependent, and reversible inhibition of platelet protease-activated receptor-1, according to a study published online Dec. 17 in Arteriosclerosis, Thrombosis, and Vascular Biology.

Paul A. Gurbel, M.D., from the Sinai Hospital of Baltimore, and colleagues report on the first human use of a protease-activated receptor-1-based pepducin, which was administered to 31 subjects with coronary artery disease or multiple coronary artery disease risk factors. The authors examined the safety, antiplatelet efficacy, and pharmacokinetics at baseline, during the first 24 hours, and at seven to 10 days after dosing.

The researchers observed dose-dependent inhibitory effects of PZ-128 on platelet aggregation, stimulated by the protease-activated receptor-1 agonist SFLLRN at 30 minutes to six hours, with 20 to 40 percent inhibition at 0.3 mg/kg, 40 to 60 percent at 0.5 mg/kg, and ≥80 to 100 percent at 1 to 2 mg/kg. The inhibitory effects of 0.5 mg/kg PZ-128 were reversible; by 24 hours, recovery of aggregation to SFLLRN was 50 percent. PZ-128 had no significant effects on aggregation induced by AYPGKF, ADP, or collagen. PZ-128 had a plasma half-life of 1.3 to 1.8 hours and was not detectable in urine.

"PZ-128 is a promising antiplatelet agent that provides rapid, specific, dose dependent, and reversible inhibition of platelet protease-activated receptor-1 through a novel intracellular mechanism," the authors write.

Several authors disclosed financial ties to the pharmaceutical and medical device industries.

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