Inhibition of PKC beta by ruboxistaurin does not enhance the acute blood pressure response to nitroglycerin.
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.
Benson
C
C
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA.
Seger
M
M
Voelker
J
J
D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000368:Aged; D000787:Angina Pectoris / Q000188:drug therapy / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects*; D002908:Chronic Disease; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007024:Hypotension, Orthostatic / Q000139:chemically induced; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008297:Male; D008301:Maleimides / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008875:Middle Aged; D005996:Nitroglycerin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D064546:Protein Kinase C beta; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D004791:Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D008301:Maleimides; D014665:Vasodilator Agents; C099154:ruboxistaurin; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D005996:Nitroglycerin