氟比洛芬酯脂微球在大鼠和比格犬体内的药动学及组织分布和排泄研究

Study on pharmacokinetics,tissue distribution and excretion of flurbiprofen axetil lipid microshpere in Sprague-Dawley rats and Beagle dogs

目的:研究氟比洛芬酯脂微球在大鼠和比格犬体内的药动学以及在大鼠体内的组织分布和排泄情况。方法:分别静注给予大鼠2 mg/kg和比格犬1 mg/kg氟比洛芬酯注射液,采用LC-MS/MS法测定给药后不同时间大鼠和比格犬血浆、组织液和排泄物中氟比洛芬的含量,并用统计矩法得到大鼠和比格犬体内的药代动力学参数。结果:静注给予大鼠和比格犬氟比洛芬酯注射液后所得到的主要药代动力学参数分别为:AUC0-∞:(43.00±6.26)和(651.53±175.89)mg·L^(-1)·h^(-1),CL:(0.047±0.007)和(0.002±0.001)L·h^(-1)·kg^(-1),t_(1/2):(5.39±0.50)和(87.18±28.58)h,MRT_(0-∞):(7.04±0.46)和(118.20±30.12)h,VZ:(0.110±0.067)和(0.119±0.068)L/kg。静注给予大鼠氟比洛芬酯注射液后,药物迅速而广泛地分布于各组织中,但组织中的药物浓度相对于血浆中较低。大鼠静脉注射给予氟比洛芬酯注射液后36 h内只有0.23%±0.10%的药物通过尿液排出体外。结论:静注给药后,氟比洛芬酯注射液在大鼠和比格犬体内的消除半衰期与氟比洛芬的其他剂型相比明显延长,说明该剂型可以延长镇痛作用的持续时间,同时药物在组织中的分布较少也可以有效地降低非甾体类抗炎药对胃肠道的副作用。

AIM： To explore the pharmacokinetic,distribution and excretion characteristics of flurbiprofen axetil in Sprague-Dawley rats and Beagle dogs. METHODS： SD rats and Beagle dogs were intravenously administrated with flurbiprofen axetil injection at the dose of 2 mg / kg and 1 mg / kg respectively. The concentration of flurbiprofen in plasma,tissues and urine were determinated by LC-MS /MS method. RESULTS： The plasma pharmacokinetic parameters of flurbiprofen in rats and dogs following intravenous administration at 2 mg / kg and 1 mg /kg depicted as： AUC0- ∞：（ 43. 00 ± 6. 26） and（ 651. 53 ± 175. 89） mg·L^-1·h^-1,CL：（ 0. 047± 0. 007） and（ 0. 002 ± 0. 001） L·h^-1·kg^-1,t1 /2：（ 5. 39 ± 0. 50） and（ 87. 18 ± 28. 58） h,MRT0- ∞：（ 7. 04 ± 0. 46） and（ 118. 20 ±30. 12） h,VZ：（ 0. 110 ± 0. 067） and（ 0. 119 ±0. 068） L / kg. In rats following flurbiprofen axetil injection,flurbiprofen was widely distributed into various tissues but with much lower concentrations compared to plasma. During the period of 36 h,the urinary accumulative excretion ratio accounted for only 0. 23% ± 0. 10%. CONCLUSION： Compared with some other dosage forms of flurbiprofen,the half-life of flurbiprofen axetil injection was longer after intravenous administration both in rats and dogs,which led to its prolonged duration of analgesic action. In addition,a minor amount of flurbiprofen was distributed into analyzed tissues,which could partly decrease the incidence of side effects.