洛伐他汀烟酸缓释片在比格犬体内的药代动力学

目的研究洛伐他汀烟酸缓释片在Beagle犬体内的药动学变化。方法6只Beagle犬采用两周期随机交叉实验设计,口服500mg洛伐他汀烟酸缓释片或烟酸片,采用反相高效液相色谱法(RP-HPLC)内标定量法测定烟酸血药浓度及药代动力学参数。结果Beagle犬口服给予洛伐他汀烟酸缓释片和烟酸片后,两者在犬体内的代谢均表现为一室模型,主要药动学参数:T12(Ke)64.99min vs.106.09min,T(peak)75.67min vs.112.20min,C(max)52.95μg.ml-1vs.28.50μg.ml-1,AUC 10831.10 vs.9086.42μg.ml-1。结论RP-HPLC内标定量测定烟酸,该方法操作简便、准确灵敏、重现性好,可用于烟酸在体内的药动学研究。单剂量口服洛伐他汀烟酸缓释片后测得的T12(Ke)、T(peak)和C(max)与烟酸组相比,差异性显著;AUC基本一致。缓释片的T12(Ke)、T(peak)明显长于烟酸片,Cmax低于烟酸片,这表明我们制备的复方洛伐他汀烟酸缓释片在Beagle犬体内具有缓释作用,相对生物利用度基本一致。

Study on pharmacokinetics of sustain-realease tablets of niacin and lovastatin in Beagle dogs

OBJECTIVE To study the variation of pharmacokinetics parameters of sustain-realease tablets of niacin and lovastatin in Beagle dogs plasma.METHODS Single dose of sustained-release niacin and lovastatin formulation(500mg) and rapid-release niacin formulation(500mg) were given to dogs.To establish a RP-HPLC method for the detemination of niacin plasma concentration and its pharmacokinetics parameters.RESULTS The pharmacokinetics of sustained-release niacin and lovastatin formulation(500mg) and rapid-release niacin formulation in Beagle dogs was fitted to one-compartment model.The main pharmacokinetics parameters of the two pharmaceutical preparation were as follows: T_1/2(Ke) 64.99min vs.106.09min,T(peak)75.67min vs.112.20min,C(max)52.95μg·ml~(-1) vs.28.50μg·ml~(-1),AUC 10831.10 vs.9086.42μg·ml~(-1).CONCLUSION The T_1/2(Ke)、T(peak) of sustained-release niacin and lovastatin formulation is significantly longer than that of the conventional niacin tablet,the C_(max) was significantly lower than that of the conventional niacin tablet.The relative bioavailability is mainly coincident.The recovery of the method showed that the method had a good selectivity,sensitivity and reproducibility and can be used for pharmacokinetics studies of niacin.