Stahlmann R, Schwabe R
Institut für Klinische Pharmakologie und Toxikologie, Universitätsklinikum Benjamin Franklin Freie Universität Berlin, Germany.
J Antimicrob Chemother. 1997 Dec;40 Suppl A:83-92. doi: 10.1093/jac/40.suppl_1.83.
Preclinical investigations with grepafloxacin showed that its toxicological profile is similar to that of other fluoroquinolones. The photosensitizing effect of grepafloxacin was relatively weak and similar to that of ciprofloxacin. Grepafloxacin did not cause convulsions in mice when administered in conjunction with the non-steroidal anti-inflammatory drug fenbufen. Intravenous injection of grepafloxacin caused transient dysrhythmias in rabbits at a dosage of 10 mg/kg and ventricular tachycardia at 30 mg/kg iv. Joint cartilage lesions were found in juvenile dogs after iv treatment with 100 mg/kg daily. Plasma concentrations (19-24 mg/L) under these conditions were approximately ten times above a therapeutic level. Data derived from patients who had been treated with grepafloxacin in phase II and phase III multiple-dose studies (400 mg, n = 1069; 600 mg, n = 925) were available for an analysis of the patients' tolerance of the drug. The most common adverse events observed for the 400 mg and 600 mg treatments during these studies were gastrointestinal reactions, such as nausea (11% and 15%, respectively), vomiting (1% and 6%) and diarrhoea (3% and 4%). In both groups a considerable number of patients (9% and 17%) reported an unpleasant taste; this was less common in the pooled controls (1%) after treatment with drugs such as doxycycline, ciprofloxacin, amoxycillin or cefixime. Headache occurred in 4% (400 mg) and 5% (600 mg) and insomnia in 1% (400 mg) or 2% (600 mg) of the patients. Similar incidences were found for photosensitivity (1% and 2%, respectively) and for rash (1% and 2%) in the 400 mg and 600 mg groups. So far, tolerance of the new compound seems to be similar to that of other fluoroquinolones. However, incidences of nausea, vomiting and unpleasant taste were rather high during the first clinical trials, particularly after treatment with 600 mg daily. Further data are necessary for a sound evaluation of the tolerance of grepafloxacin.
格帕沙星的临床前研究表明，其毒理学特征与其他氟喹诺酮类药物相似。格帕沙星的光敏作用相对较弱，与环丙沙星相似。格帕沙星与非甾体抗炎药芬布芬联合给药时，在小鼠中未引起惊厥。静脉注射格帕沙星，剂量为10mg/kg时，在兔中引起短暂性心律失常，剂量为30mg/kg静脉注射时引起室性心动过速。幼年犬每日静脉注射100mg/kg治疗后出现关节软骨损伤。在这些条件下的血浆浓度（19 - 24mg/L）约比治疗水平高10倍。在II期和III期多剂量研究（400mg，n = 1069；600mg，n = 925）中接受格帕沙星治疗的患者数据可用于分析患者对该药物的耐受性。在这些研究中，400mg和600mg治疗组观察到的最常见不良事件是胃肠道反应，如恶心（分别为11%和15%）、呕吐（1%和6%）和腹泻（3%和4%）。两组中相当数量的患者（9%和17%）报告有异味；在用多西环素、环丙沙星、阿莫西林或头孢克肟等药物治疗后的合并对照组中（1%）这种情况较少见。4%（400mg）和5%（600mg）的患者出现头痛，1%（400mg）或2%（600mg）的患者出现失眠。400mg和600mg组的光敏反应（分别为1%和2%）和皮疹（1%和2%）发生率相似。到目前为止，新化合物的耐受性似乎与其他氟喹诺酮类药物相似。然而，在首次临床试验期间，恶心、呕吐和异味的发生率相当高，尤其是每日服用600mg治疗后。需要进一步的数据来全面评估格帕沙星的耐受性。
