甲苯磺酸妥舒沙星滴眼液开封挑战试验

目的:评价甲苯磺酸妥舒沙星滴眼液在开封使用过程中抗环境微生物污染能力。方法:将供试品随机分组,开盖后暴露于普通室内环境,分别在不同时间段随机抽取样品进行微生物限度检查,结合监测到的环境微生物进行结果分析。结果:160支供试品试验前后微生物限度检查结果无显著差异,受环境菌污染而发生的阳性率低于对照组。结论:甲苯磺酸妥舒沙星滴眼液在开封使用期内可有效抵抗环境微生物的污染。     

复方妥舒沙星鼻用喷雾剂的研制

目的：制备复方妥舒沙星鼻用喷雾荆并建立质量控制方法。方法：拟定处方组成及制备工艺；采用紫外分光光度法测定妥舒沙星含量；采用旋光法测定盐酸麻黄碱含量。结果：妥舒沙星在4．5—63．0μg·ml^-1范围内线性关系良好，r=0．9999。平均回收率为99．7％，RSD为0．48％。结论：该制剂制备工艺简单，质量控制方法可靠，质量稳定。     

国产妥舒沙星片与进口妥舒沙星片人体生物等效性研究

目的　进行国产妥舒沙星片与进口妥舒沙星片的人体生物等效性研究。方法　 12名健康志愿者随机自身交叉给药 ,分别单次口服 3 0 0mg国产妥舒沙星片与进口片剂 ,采用高效液相色谱紫外检测法 ,测定血浆及尿液中药物浓度。经 3p97药代动力学计算程序处理计算参数 ,并进行双单侧t检验确定是否生物等效。结果　该药体内过程符合口服给药一室模型 ,国产片与进口片的主要药代动力学参数分别为Tmax(1.188± 0 .43 9)和 (1.3 3 2± 0 .5 81)h ,Cmax(1.5 0 1± 0 .5 96)和 (1.3 45± 0 .5 0 6)mg/L ,AUC0 -∞(8.845± 3 .410 )和 (8.971±3 .3 87)mg·h/L ,用梯形法计算所得的AUC0 -t分别为 (10 .13 3± 3 .92 7)和 (9.80 3± 3 .3 43 )mg·h/L ,由AUC0 -t计算国产片的相对生物利用度为 (10 2 .5± 13 .6) %。结论　两种制剂具有生物等效性。     

Stereoselective analysis of the disposition of tosufloxacin enantiomers in man

Summary The pharmacokinetics of tosufloxacin enantiomers after oral administration of racemic tosufloxacin were examined in healthy volunteers. Only small differences were observed in time to peak concentration (2.6±0.3 [mean ± SEM] h for (+)-tosufloxacin vs 2.4±0.2 h for (–)-tosufloxacin), elimination half-life (3.61±0.24 h vs 3.49±0.23 h), and area under the curve (2.78±0.19 h·g/ml vs 2.87±0.19 h·g/ml); however, peak concentration (0.40±0.03 g/ml vs 0.44±0.03 g/ml), renal clearance (226±10 ml/min vs 202±10 ml/min), and urinary recovery (35.4±2.2% vs 32.4±1.9%) differed significantly between enantiomers.     

妥舒沙星对家兔体内氨茶碱药动学的研究

目的:研究妥舒沙星对家兔氨茶碱药动学的影响。方法:将18只家兔随机等分为A、B、C三组,A组经耳缘iv给予单剂量氨茶碱12．5 mg·kg-1;B、C两组家兔分别灌服妥舒沙星(每日300 mg·kg-1及450 mg·kg-1,分3次灌服),共服3 d,于第4天灌服妥舒沙星1 h后,iv与A组相同剂量的氨茶碱。结果:A、B、C三组的K分别为:0．1753,0．1341,0．1280 h-1;t1/2: 3．847,4．885,5．766 h;Vd:0．543,0．534,0．524 L;CL:0．0979,0．0759,0．0630 L·h-1;AUC:125．4,167．9,200．2μg·h·ml-1。结论:妥舒沙星使茶碱的K降低,t1/2延长,AUC增大,CL下降,对茶碱代谢的影响呈剂量依赖性。临床上妥舒沙星与氨茶碱合用时应监测茶碱的血药浓度,及时调整氨茶碱的剂量,以免引起氨茶碱中毒。     

妥舒沙星前药的合成及其体内抗菌活性

分别以N-叔丁氧羰基-L-亮氨酸(L-缬氨酸)和妥舒沙星盐酸盐为原料,经缩合后在盐酸中水解得到含有L-亮氨酰基或L-缬氨酰基的2种妥舒沙星前药的盐酸盐(1a,b)。测定了它们及对照药对小鼠腹腔感染不同细菌的体内保护疗效,结果表明,1b对肺炎链球菌9798和金葡球菌15的体内活性均弱于对甲苯磺酸妥舒沙星(TSFX·TosOH);1a对肺炎链球菌9798、金葡球菌15和金葡球菌01193的体内活性均强于TSFX·TosOH。1a具有潜在的开发价值,值得进一步深入评价。     

Pharmacodynamic evaluation of tosufloxacin against Streptococcus pneumoniae in an in vitro model simulating serum concentration

We compared the antibacterial effects and the emergence of resistance to tosufloxacin or levofloxacin for Streptococcus pneumoniae by simulating the serum concentration according to the Japanese clinical regimens using an in vitro pharmacokinetic-pharmacodynamic model. For quinolone-susceptible strain ATCC49619, tosufloxacin showed bactericidal activity, given that both the AUC_0–24h/MIC ratios at the dosage of 150 mg t.i.d. and 300 mg b.i.d. of tosufloxacin tosilate were 138 and 193, and the C_max/MIC ranges were 7.93–10.2 and 15.9–17.6, respectively, which were greater than those of levofloxacin (100 mg t.i.d. and 200 mg b.i.d.). The greater area above the killing curves (AAKCs) or shorter time to achieve 99.9% killing (99.9% KT) in both models of tosufloxacin than those of levofloxacin was related to their larger AUC_0–24h/MIC and C_max/MIC. Exposure of only 100 mg t.i.d. of levofloxacin led to outgrowth of the parC mutants, which were twofold less susceptible to levofloxacin than the parent strain. Neither of the tosufloxacin tosilate regimens resulted in isolation of resistant mutants of this strain. For the parC mutant strain D-3197, both the AUC_0–24h/MIC and C_max/MIC ratios of tosufloxacin were greater than those of levofloxacin, which resulted in comparable or better bactericidal activity as compared to those of levofloxacin. However, both fluoroquinolones and both regimens led to outgrowth of resistant mutants, which possessed a mutation in gyrA in addition to parC. In conclusion, tosufloxacin is superior to levofloxacin in bactericidal activity against S. pneumoniae in the Japanese clinical regimens, especially in the quinolone-susceptible strain, without emergence of resistant subpopulations.     

Antimicrobial activities of tosufloxacin against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella branhamella catarrhalis isolated from otolaryngological infectious diseases

In 2003, the Japan Society for Infectious Diseases in Otolaryngology conducted its third nationwide survey of clinical isolates from otolaryngological infectious diseases. We selected three primary causative organisms of otolaryngological infectious diseases, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella Branhamella catarrhalis, and evaluated their sensitivities to tosufloxacin (TFLX), a new oral quinolone, because the survey revealed a rise in drug-resistant strains, suggesting potential problems with the antibiotics commonly used against these organisms. The minimum inhibitory concentration (MIC)₉₀ values of TFLX against S. pneumoniae, H. influenzae, and M. catarrhalis were 0.25 μg/ml, ≤0.06 μg/ml, and ≤0.06 μg/ml respectively, and TFLX was shown to be as effective as or superior to other new quinolones. In addition, TFLX showed sufficient antimicrobial effects against frequently detected drug-resistant bacteria such as penicillin-resistant S. pneumoniae (PRSP) and β-lactamase-negative, ampicillin-resistant strains of H. influenzae (BLNAR). Furthermore, only a few strains of bacteria showed resistance to TFLX.     

复方妥舒沙星滴耳液的制备及质量控制

目的制备复方妥舒沙星滴耳液并建立质量控制方法.方法采用紫外分光光度法测定妥舒沙星含量.结果妥舒沙星在10～60μg·mL-1浓度范围内,线性关系良好,r=0.999 9.平均回收率为99.90%,RSD为1.01%(n=9).结论本制剂制备工艺简便可行,质量稳定可控.