Abstract
Ruboxistaurin is a selective protein kinase C beta inhibitor undergoing clinical investigation for treatment of diabetic microvascular complications. This study assessed a possible blood pressure (BP) interaction between ruboxistaurin and the exogenous nitric oxide donor, glyceryl trinitrate (GTN). Subjects (N=22) with chronic stable angina received placebo or ruboxistaurin 96 mg/day orally to steady state in a crossover design. Graded GTN (0, 5, 10, 20, 40, 80, and 120 microg/min) or 5% dextrose solution was then infused intravenously and BP was measured following each dose. Ruboxistaurin did not alter the slope of change in standing systolic BP (DeltasSBP/1n[GTN dose]) curve (P=0.272 analysis of covariance) or affect the DeltasSBP at the estimated GTN dose producing a 10-mm Hg reduction in sSBP from baseline on placebo (mean difference -0.9 mm Hg; 95% confidence of interval, -3.3-1.5). In conclusion, ruboxistaurin does not potentiate the acute BP-lowering effects of GTN.
Publication types
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Randomized Controlled Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Oral
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Adrenergic beta-Antagonists / therapeutic use
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Aged
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Angina Pectoris / drug therapy
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Angina Pectoris / physiopathology
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Blood Pressure / drug effects*
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Chronic Disease
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Cross-Over Studies
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Dose-Response Relationship, Drug
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Double-Blind Method
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Drug Administration Schedule
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Drug Interactions
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Enzyme Inhibitors / administration & dosage
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Enzyme Inhibitors / adverse effects
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Enzyme Inhibitors / pharmacology
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Female
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Humans
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Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
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Hypotension, Orthostatic / chemically induced
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Indoles / administration & dosage
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Indoles / adverse effects
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Indoles / pharmacology*
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Infusions, Intravenous
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Male
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Maleimides / administration & dosage
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Maleimides / adverse effects
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Maleimides / pharmacology*
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Middle Aged
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Nitroglycerin / administration & dosage
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Nitroglycerin / adverse effects
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Nitroglycerin / pharmacology*
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Protein Kinase C / antagonists & inhibitors*
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Protein Kinase C beta
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Treatment Outcome
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Vasodilator Agents / administration & dosage
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Vasodilator Agents / adverse effects
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Vasodilator Agents / pharmacology
Substances
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Adrenergic beta-Antagonists
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Enzyme Inhibitors
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Hydroxymethylglutaryl-CoA Reductase Inhibitors
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Indoles
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Maleimides
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Vasodilator Agents
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ruboxistaurin
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Protein Kinase C
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Protein Kinase C beta
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Nitroglycerin