Gauhar Shahnaz, Ali Syed Ayub, Naqvi Syed Baqir, Shoaib Muhammad Harris
College of Pharmaceutical Sciences, RAK Medical and Health Sciences University, Ras Al Khaimah, UAE.
Department of Pharmaceutics, Faculty of Pharmacy, University of Karachi, Pakistan.
Pak J Pharm Sci. 2014 Mar;27(2):389-95.
In the present study, the pharmacokinetic and drug interaction evaluation of two drugs pefloxacin and paracetamol was carried out by a single-dose, two-treatment and two-sequence crossover design. Total fifteen healthy volunteers participated out of which ten completed the study. All were male volunteers, aged 22.36 years (means), with a mean weight of 76.45±12.05 Kg. The washout period between treatments was 5 week. Initially the method utilized for quantitative analysis of the drug was developed which was further validated. The study involved plasma protein precipitation with ethyl acetate and detection was done at 275nm. The retention time for pefloxacin 18±1 min and paracetamol were approximately 6±1 min, respectively. The calibration curve for pefloxacin was linear in the concentration range of 0.125-12.0mg/ml with r(2)=0.9987 in plasma. Standard concentration solution was maintained on the same temperature as that of volunteer's samples to optimize the periods for the determination of drug concentration in the plasma samples. Blood samples were collected from volunteers at different time intervals. The pharmacokinetics and drug interaction studies were anticipated by plotting concentration versus time-profiles. The value of AUC0-∞ in control was 67.355±3.174μg.h/ml, in treatment 61.242±3.868μg.h/ml along with relative bioavailability =91.395±4.864. Under the control and treatment condition the mean maximum plasma concentrations were found to be 4.679±0.248 μg/ml and 4.6595±0.266 μg/ml respectively. The average T(max) for plasma concentrations was 1.819±0.1743hr and 1.605 ±0.1134hr respectively. The biological half-lives in the two phases of studies were found to be 7.953±0.33hr in control and 7.7257±0.355hr in treatment. No significant effect were observed on the bioavailability and pharmacokinetics of pefloxacin by the concomitant administration with paracetamol, however very minor effect were observed that might be related with inter-individual variation in human volunteers. This pharmacokinetic studies also indicated that the level of drug (Cmax) do not differ from previous studies in different races.
在本研究中，采用单剂量、双治疗、双序列交叉设计对两种药物培氟沙星和对乙酰氨基酚进行了药代动力学和药物相互作用评估。共有15名健康志愿者参与，其中10人完成了研究。所有志愿者均为男性，平均年龄22.36岁，平均体重76.45±12.05千克。治疗之间的洗脱期为5周。最初开发了用于药物定量分析的方法，并进一步进行了验证。该研究采用乙酸乙酯进行血浆蛋白沉淀，并在275nm处进行检测。培氟沙星的保留时间为18±1分钟，对乙酰氨基酚的保留时间约为6±1分钟。培氟沙星在血浆中的校准曲线在0.125 - 12.0mg/ml浓度范围内呈线性，r(2)=0.9987。将标准浓度溶液保持在与志愿者样品相同的温度下，以优化血浆样品中药物浓度测定的时间。在不同时间间隔从志愿者采集血样。通过绘制浓度与时间曲线来预测药代动力学和药物相互作用研究。对照组中AUC0-∞的值为67.355±3.174μg.h/ml，治疗组中为61.242±3.868μg.h/ml，相对生物利用度=91.395±4.864。在对照和治疗条件下，平均最大血浆浓度分别为4.679±0.248μg/ml和4.6595±0.266μg/ml。血浆浓度的平均T(max)分别为1.819±0.1743小时和1.605±0.1134小时。在两个研究阶段中，生物半衰期在对照组中为7.953±0.33小时，在治疗组中为7.7257±0.355小时。与对乙酰氨基酚联合给药对培氟沙星的生物利用度和药代动力学未观察到显著影响，但观察到非常轻微的影响，这可能与人类志愿者的个体差异有关。该药代动力学研究还表明，药物水平（Cmax）与之前不同种族的研究无差异。
