Takasuna K, Kasai Y, Kitano Y, Mori K, Kobayashi R, Makino M, Hagiwara T, Hirohashi M, Nomura M, Algate D R
Drug Safety Research Center, Developmental Research Laboratories, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
J Toxicol Sci. 1995 Oct;20 Suppl 1:133-51. doi: 10.2131/jts.20.supplementi_133.
The general pharmacological study of iodixanol, a non-ionic isotonic contrast medium, was conducted. 1) Iodixanol administered intravenously over a dose range of 320 to 3,200 mgI/kg had little or no effect on the general behavior, spontaneous locomotor activity, hexobarbital sleeping time, pain response, electroshock- or pentylenetetrazol-induced convulsion (mouse), EEG or body temperature (rabbit), gastrointestinal propulsion (mouse) or skeletal muscle contraction (rabbit). Iodixanol had no specific interaction with acetylcholine, histamine, serotonin, nicotin, BaCl2 (ileum), methacholine (trachea), isoprenaline (atrium) or oxytocin (pregnant uterus), nor had any effect on spontaneous contractility (atrium and uterus), or transmural electrostimulation-induced contractility (vas deferens) at concentrations of < or = 3.2 x 10(-3) gI/ml in vitro. Iodixanol had no effect on the cardiovascular system of dog, except that it increased femoral blood flow and respiratory rate at doses of > or = 1,000 mgI/kg. Iodixanol at 3,200 mgI/kg i.v. reduced urine output with a decrease in Na+ and Cl- excretion, whereas at 320 mgI/kg i.v., it slightly increased urine output (rat). 2) Injections of iodixanol into the cerebroventricular (0.96, 9.6 mgI/mouse and 3.2, 32 mgI/rat), left ventricular (1,920, 6,400 mgI/dog) or coronary artery (640, 1,920 mgI/dog) had no conspicuous effect on the central nervous system or the cardiovascular system, respectively. There was no marked difference among iodixanol, iohexol and iopamidol in this respect. Vascular pain during injection into the femoral artery (300-320 mgI/guinea pig) appeared to be less intense with iodixanol, compared with the other contrast media iohexol and iopamidol. These results suggest that intravenous injection of iodixanol is relatively free from pharmacological activity, and effects of iodixanol on the central nervous system (intracerebroventricular injection) and cardiovascular system (intra-left ventricular and -coronary injections) are comparable to those of iohexol and iopamidol. Furthermore, intra-femoral injection of iodixanol has less of a tendency to produce vascular pain than those of iohexol and iopamidol.
对非离子等渗造影剂碘克沙醇进行了一般药理学研究。1）静脉注射剂量范围为320至3200mgI/kg的碘克沙醇，对一般行为、自发运动活性、己巴比妥睡眠时间、疼痛反应、电休克或戊四氮诱导的惊厥（小鼠）、脑电图或体温（兔）、胃肠推进（小鼠）或骨骼肌收缩（兔）几乎没有影响。碘克沙醇与乙酰胆碱、组胺、5-羟色胺、烟碱、氯化钡（回肠）、乙酰甲胆碱（气管）、异丙肾上腺素（心房）或催产素（妊娠子宫）没有特异性相互作用，在体外浓度≤3.2×10⁻³gI/ml时，对自发收缩性（心房和子宫）或跨膜电刺激诱导的收缩性（输精管）也没有任何影响。碘克沙醇对犬的心血管系统没有影响，除非剂量≥1000mgI/kg时会增加股血流量和呼吸频率。静脉注射3200mgI/kg的碘克沙醇会使尿量减少，同时钠和氯排泄减少，而静脉注射320mgI/kg时，尿量会略有增加（大鼠）。2）向脑室（0.96、9.6mgI/小鼠和3.2、32mgI/大鼠）、左心室（1920、6400mgI/犬）或冠状动脉（640、1920mgI/犬）注射碘克沙醇，分别对中枢神经系统或心血管系统没有明显影响。在这方面，碘克沙醇、碘海醇和碘帕醇之间没有显著差异。与其他造影剂碘海醇和碘帕醇相比，向股动脉注射碘克沙醇（300 - 320mgI/豚鼠）时血管疼痛似乎较轻。这些结果表明，静脉注射碘克沙醇相对没有药理活性，碘克沙醇对中枢神经系统（脑室内注射）和心血管系统（左心室内和冠状动脉内注射）的影响与碘海醇和碘帕醇相当。此外，股动脉内注射碘克沙醇产生血管疼痛的倾向比碘海醇和碘帕醇小。
