Marier Jean-Francois, Ducharme Murray P, DiMarco Marika, Di Spirito Mike, Morelli Gaetano, Tippabhotla Sudhakar K, Badri N, Rampal Ashok, Monif Tausif
PK/PD Department, MDS Pharma Services, St-Laurent, Québec, Canada.
Clin Ther. 2006 Dec;28(12):2070-80. doi: 10.1016/j.clinthera.2006.12.018.
Ofloxacin is a fluoroquinolone agent available as an immediate-release (IR) tablet formulation administered twice daily. An extended-release (ER) formulation of ofloxacin has been developed for oncedaily administration.
The present studies compared the pharmacokinetic (PK) and safety profiles of the ER and IR formulations of ofloxacin.
Based on specific inclusion and exclusion criteria, healthy adult male and female volunteers were selected to receive single and multiple oral doses of ofloxacin ER 400 mg QD and ofloxacin IR 200 mg BID in 2 separate open-label, randomized, crossover studies. Multiple blood samples were collected, and plasma concentrations of ofloxacin were analyzed using a high-throughput liquid chromatography system. PK parameters were calculated using noncompartmental methods. Safety was assessed in the clinical pharmacology unit based on vital signs, electrocardiograms (ECGs), and reported adverse events. The relationship of an adverse event to study drugs (definitely, probably, possibly, remotely, or unrelated) was assessed by the principal investigator.
Forty healthy subjects were included in each study. Thirty-seven subjects (28 men, 9 women; mean age, 37 years; mean weight, 71.2 kg) completed the single-dose study, and 38 subjects (33 men, 5 women; mean age, 36 years; mean weight, 72.2 kg) completed the multiple-dose study. With the exception of 3 black subjects in each study of African-American origin, all subjects in both studies were white. The mean AUC(0-24) values for the ER formulation in the single-and multiple-dose studies (18.6 and 21.4 mg . h/L, respectively) were similar to those for the IR formulation (17.7 and 22.8 mg x h/L), with the 90% CIs falling between 80.0 and 125.0. Mean C(max) values for the ER formulation in the single- and multiple-dose studies (2.02 and 2.12 mg/L) were also similar to those for the IR formulation (1.74 and 1.85 mg/L). Under steady-state conditions, median T(max) values for the ER formulation were significantly longer than those for the IR formulation (5.00 vs 2.00 hours, respectively; P < 0.05). All vital signs and ECGs were within normal ranges during the single- and multipledose studies. Adverse events probably related to study drugs (eg, nausea, loose stools, emesis) were similar in nature and frequency between the 2 formulations. No serious adverse events were reported during either study.
In these 2 trials in a selected group of healthy adult male and female volunteers, the ER and IR formulations of ofloxacin displayed a similar rate and extent of bioavailability and comparable safety profiles.
氧氟沙星是一种氟喹诺酮类药物，有速释（IR）片剂剂型，每日给药两次。已开发出氧氟沙星的缓释（ER）剂型用于每日一次给药。
本研究比较了氧氟沙星ER和IR剂型的药代动力学（PK）和安全性。
根据特定的纳入和排除标准，选择健康成年男性和女性志愿者，在两项单独的开放标签、随机、交叉研究中，分别接受单次和多次口服400mg每日一次的氧氟沙星ER和200mg每日两次的氧氟沙星IR。采集多份血样，使用高通量液相色谱系统分析血浆中氧氟沙星的浓度。使用非房室方法计算PK参数。在临床药理学单元根据生命体征、心电图（ECG）和报告的不良事件评估安全性。主要研究者评估不良事件与研究药物的关系（肯定、很可能、可能、不太可能或无关）。
每项研究纳入40名健康受试者。37名受试者（28名男性，9名女性；平均年龄37岁；平均体重71.2kg）完成了单剂量研究，38名受试者（33名男性，5名女性；平均年龄36岁；平均体重72.2kg）完成了多剂量研究。除每项研究中有3名非裔美国裔黑人受试者外，两项研究中的所有受试者均为白人。单剂量和多剂量研究中ER剂型的平均AUC(0 - 24)值（分别为18.6和21.4mg·h/L）与IR剂型的相似（17.7和22.8mg x h/L），90%置信区间在80.0至125.0之间。单剂量和多剂量研究中ER剂型的平均C(max)值（2.02和2.12mg/L）也与IR剂型的相似（1.74和1.85mg/L）。在稳态条件下，ER剂型的中位T(max)值明显长于IR剂型（分别为5.00小时和2.00小时；P < 0.05）。在单剂量和多剂量研究期间，所有生命体征和心电图均在正常范围内。两种剂型中可能与研究药物相关的不良事件（如恶心、稀便、呕吐）在性质和频率上相似。两项研究均未报告严重不良事件。
在这两项针对选定的健康成年男性和女性志愿者的试验中，氧氟沙星的ER和IR剂型显示出相似的生物利用度速率和程度以及相当的安全性。
