Czyrski Andrzej, Kondys Katarzyna, Szałek Edyta, Karbownik Agnieszka, Grześkowiak Edmund
Department of Physical Pharmacy and Pharmacokinetics, Poznań University of Medical Sciences, Poznań, Poland.
Department of Physical Pharmacy and Pharmacokinetics, Poznań University of Medical Sciences, Poznań, Poland.
Pharmacol Rep. 2015 Jun;67(3):542-4. doi: 10.1016/j.pharep.2014.12.013. Epub 2014 Dec 31.
The aim of this study was to evaluate the impact of sunitinib on pharmacokinetics of levofloxacin. The previous study proved that levofloxacin co-administered with sunitib changes the following pharmacokinetic parameters i.e. Cmax and AUC for both sunitinib and SU012662 (sunitinib metabolite). We will also investigate if the limited sample strategy can be applied for levofloxacin.
Rabbits were divided into two groups. In both groups there were six animals. In the control group levofloxacin was administered and in investigated group levofloxacin and sunitinib were co-administered. The dose of levofloxacin was 20mg/kg and the dose of sunitinib was 25mg. The concentration in plasma was determined by HPLC-FLD. The pharmacokinetic parameters were evaluated by WinNonLin software. The results were evaluated by the following statistical tests: Shapiro-Wilk, t-Student and Mann-Whitney test.
Pharmacokinetics of levofloxacin obeys the two-compartment model. Sunitinib influences the following pharmacokinetic parameters of levofloxacin: half-life, elimination constant and volume of distribution. Statistical analysis proved that there is a correlation between AUC and the following five time-points: 0.25 h, 4h, 6h, 10h and 12h.
The study proved that there is a potential pharmacokinetic interaction between sunitinib and levofloxacin. The statistical analysis proved that the limited sample strategy can be applied for levofloxacin.
本研究的目的是评估舒尼替尼对左氧氟沙星药代动力学的影响。先前的研究证明，左氧氟沙星与舒尼替尼联合使用会改变舒尼替尼和SU012662（舒尼替尼代谢物）的以下药代动力学参数，即Cmax和AUC。我们还将研究有限样本策略是否可应用于左氧氟沙星。
将兔子分为两组。两组各有六只动物。对照组给予左氧氟沙星，研究组给予左氧氟沙星和舒尼替尼。左氧氟沙星的剂量为20mg/kg，舒尼替尼的剂量为25mg。采用高效液相色谱-荧光检测法测定血浆浓度。用WinNonLin软件评估药代动力学参数。结果通过以下统计检验进行评估：Shapiro-Wilk检验、t检验和Mann-Whitney检验。
左氧氟沙星的药代动力学符合二室模型。舒尼替尼影响左氧氟沙星的以下药代动力学参数：半衰期、消除常数和分布容积。统计分析证明，AUC与以下五个时间点之间存在相关性：0.25小时、4小时、6小时、10小时和12小时。
该研究证明舒尼替尼与左氧氟沙星之间存在潜在的药代动力学相互作用。统计分析证明有限样本策略可应用于左氧氟沙星。
