title: Acute effects of thromboxane dual blocker (KDI-792) on different portions of lower limb blood flow--a study using Doppler ultrasonography and laser Doppler flowmetry in type 2 diabetic patients.
abstract: The acute effects of a newly synthesized thromboxane dual blocker (KDI-792), a combined thromboxane synthase inhibitor and receptor antagonist, on lower limb circulation were examined using two-dimensional color and pulse Doppler ultrasonography and laser Doppler flowmetry. A randomized single-masked, placebo-controlled trial was performed on 36 type 2 diabetic patients with minimally impaired baseline flow. The anatomical cross-sectional area (CSA), maximum flow velocity (MFV) and flow volume index (FVI) in the right dorsal pedis artery (DPA) and right femoral artery (FA) were determined by Doppler ultrasonography before and 45 and 90 minutes after the administration of either 100 or 200 mg of KDI-792 to the dose groups or placebo to the control group. Periflux blood flow (PBF) in the right foot was determined simultaneously by laser Doppler flowmetry. Both CSA and MFV in the dose groups were significantly increased in both the FA and DPA. FVI was markedly increased from 21.4 +/- 3.7 to 68.3 +/- 26.8 in the DPA (M +/- SD, P < 0.01) and from 365.4 +/- 35.3 to 771.7 +/- 75.7 in the FA (P < 0.01) in the 200 mg dose group. In the 100 mg dose group, FVI was markedly increased from 20.0 +/- 8.7 to 68.3 +/- 26.8 (P < 0.01) in the DPA and from 372.5 +/- 130.0 to 677.5 +/- 187.8 (P < 0.01) in the FA. PBF was also increased in both dose groups (from 4.15 +/- 1.4 to 7.0 +/- 4.0 ml/min/100 g tissue in the 200 mg dose group, P < 0.01), whereas there were no significant changes in either measurement in the control group. There were no significant changes in pulse rate or blood pressure after administration in either the dosage group or the placebo group. These and previous findings indicate that a single administration of KDI-792 markedly increases lower limb blood flow and might have a more potent vasodilating effect than that of prostaglandin I2 derivatives.
authors.affiliation: Department of Internal Medicine, University of Tsukuba, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Sone
authors.forename: Y
authors.initials: Y
authors.lastname: Okuda
authors.forename: Y
authors.initials: Y
authors.lastname: Tsurushima
authors.forename: M
authors.initials: M
authors.lastname: Asano
authors.forename: S
authors.initials: S
authors.lastname: Suzuki
authors.forename: Y
authors.initials: Y
authors.lastname: Kawakami
authors.forename: K
authors.initials: K
authors.lastname: Yamashita
mesh_terms: D000368:Aged; D001783:Blood Flow Velocity; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000188:drug therapy / Q000209:etiology; D003929:Diabetic Neuropathies / Q000150:complications; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005528:Foot / Q000098:blood supply*; D006801:Humans; D007700:Kinetics; D017078:Laser-Doppler Flowmetry; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D018615:Ultrasonography, Doppler, Color; D018617:Ultrasonography, Doppler, Pulsed
chemical_list: D004791:Enzyme Inhibitors; C096828:KDI 792; D010919:Placebos; D011725:Pyridines; D011759:Pyrrolidines; D017482:Receptors, Thromboxane; D013930:Thromboxane-A Synthase