Kim Mi Jo, Lim Hyeong-Seok, Cho Sang-Heon, Bae Kyun-Seop
Department of Clinical Pharmacology, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea.
Clin Drug Investig. 2014 Mar;34(3):195-201. doi: 10.1007/s40261-013-0164-z.
Gemifloxacin is a synthetic fluoroquinolone antimicrobial agent, which has potent activity against most Gram-negative and Gram-positive organisms. It is indicated for the treatment of community-acquired pneumonia and acute bacterial exacerbation of chronic bronchitis.
The aim of this study was to assess the clinical potential of a new gemifloxacin 200 mg intravenous formulation by comparing its pharmacokinetic characteristics with those of the branded Factive(®) gemifloxacin tablet.
A single-dose, open-label, randomized-sequence, two-period crossover study was performed with 17 healthy male volunteers. The two treatment periods were separated by a 1-week washout period. Blood samples were taken for up to 48 h post-dose. Plasma gemifloxacin concentrations were determined by a validated high-performance liquid chromatography-tandem mass spectrometry method. To calculate the pharmacokinetic parameters, noncompartmental analysis was performed. The two formulations were considered to be pharmacokinetically equivalent if the 90 % confidence intervals (CIs) of the log-transformed ratios (intravenous/oral formulations) of the area under the plasma concentration-time curve (AUC) from time zero to the time of the last measurable concentration (AUClast) and the AUC from time zero to infinity (AUC∞) were within the standard bioequivalence range (0.8-1.25). Safety and tolerability were evaluated on the basis of physical examinations, vital signs, electrocardiograms, clinical laboratory tests and adverse event monitoring.
Seventeen subjects were enrolled, and 15 subjects completed the study. Sixteen subjects received intravenous 200 mg gemifloxacin and 15 received oral 320 mg gemifloxacin. The 15 subjects in the pharmacokinetic analysis set had a mean (standard deviation [SD]) age, height and weight of 27.2 (5.3) years, 173.5 (4.4) cm and 67.3 (7.4) kg, respectively. Both formulations had similar pharmacokinetic profiles. For the intravenous formulation, the mean (SD) AUClast, AUC∞ and maximum plasma concentration (C max) values were 9.12 (4.03) μg·h/mL, 9.26 (4.07) μg·h/mL and 2.90 (1.65) μg/mL, respectively, while these values for the oral formulation were 9.44 (3.34) μg·h/mL, 9.60 (3.49) μg·h/mL and 2.03 (0.95) μg/mL, respectively. For the intravenous and oral formulations, the median (range) time to reach C max (t max) values were 0.9 (0.7-1.0) and 1.0 (0.5-2.0) h, respectively. The mean relative bioavailability was 68.99 %. The 90 % CI of the ratios of the log-transformed values of AUClast and AUC∞ was 0.82-1.07. There were no serious adverse events. The intravenous and oral formulations were associated with treatment-emergent adverse event incidences of 63 % (10/16) and 13 % (2/15), respectively. After the intravenous formulation was administered, application site pain and paraesthesia were the most frequently reported adverse events (31 and 25 %, respectively). All adverse events resolved spontaneously without treatment.
Intravenous 200 mg and oral 320 mg formulations of gemifloxacin are equivalent in terms of AUC following a single dose in healthy male subjects.
吉米沙星是一种合成的氟喹诺酮类抗菌药物，对大多数革兰氏阴性菌和革兰氏阳性菌具有强大的活性。它适用于治疗社区获得性肺炎和慢性支气管炎急性细菌感染。
本研究旨在通过比较新的200mg吉米沙星静脉制剂与品牌药法罗适（Factive®）吉米沙星片的药代动力学特征，评估其临床应用潜力。
对17名健康男性志愿者进行了一项单剂量、开放标签、随机序列、两周期交叉研究。两个治疗周期之间间隔1周的洗脱期。给药后长达48小时采集血样。采用经过验证的高效液相色谱 - 串联质谱法测定血浆吉米沙星浓度。通过非房室分析计算药代动力学参数。如果从零时到最后可测浓度时间的血浆浓度 - 时间曲线下面积（AUClast）以及从零到无穷大的AUC（AUC∞）的对数转换比值（静脉注射/口服制剂）的90%置信区间（CI）在标准生物等效性范围内（0.8 - 1.25），则认为两种制剂在药代动力学上等效。根据体格检查、生命体征、心电图、临床实验室检查和不良事件监测评估安全性和耐受性。
共纳入17名受试者，15名受试者完成研究。16名受试者接受静脉注射200mg吉米沙星，15名受试者接受口服320mg吉米沙星。药代动力学分析组中的15名受试者的平均（标准差[SD]）年龄、身高和体重分别为27.2（5.3）岁、173.5（4.4）cm和67.3（7.4）kg。两种制剂具有相似的药代动力学特征。对于静脉制剂，平均（SD）AUClast、AUC∞和最大血浆浓度（Cmax）值分别为9.12（4.03）μg·h/mL、9.26（4.07）μg·h/mL和2.90（1.65）μg/mL，而口服制剂的这些值分别为9.44（3.34）μg·h/mL、9.60（3.49）μg·h/mL和2.03（0.95）μg/mL。对于静脉制剂和口服制剂，达到Cmax（tmax）值的中位数（范围）时间分别为0.9（0.7 - 1.0）小时和1.0（0.5 - 2.0）小时。平均相对生物利用度为68.99%。AUClast和AUC∞对数转换值的比值的90%CI为0.82 - 1.07。未发生严重不良事件。静脉制剂和口服制剂的治疗中出现的不良事件发生率分别为63%（10/16）和13%（2/15）。静脉制剂给药后，注射部位疼痛和感觉异常是最常报告的不良事件（分别为31%和25%）。所有不良事件未经治疗均自行缓解。
在健康男性受试者中，单剂量给药后，200mg静脉制剂和320mg口服制剂的AUC方面等效。
