目的研究鞘内注射亚胺培南/西司他丁后家兔体内的药代动力学特点。方法家兔用20.0%乌拉坦耳缘静脉麻醉,给药方式为鞘内注射和静脉给药两种,每种给药方式分为低(0.35mg/kg)、中(0.7mg/kg)、高(1.4mg/kg)3种剂量组,亚胺培南/西司他丁组给药后于0、15、30min、1、2、4、8、12、24h抽取小脑延髓池脑脊液,并测定中剂量组给药后15min、2、8h的组织分布;HPLC测定脑脊液及组织中亚胺培南/西司他丁的浓度,DAS软件分析药代动力学参数。结果鞘内注射低、中、高剂量的亚胺培南/西司他丁后,脑脊液中药物分布半衰期(t1/2α)分别为(27.56±7.25)、(27.22±5.7)、(28.08±8.37)h,消除半衰期(t1/2β)分别为(26.67±3.58)、(28.23±9.23)、(29.94±6.21)h;静脉给药3种剂量后,脑脊液中药物分布半衰期分别为(6.88±0.55)、(8.25±0.24)、(7.34±0.21)h,消除半衰期(t1/2β)分别为(6.96±0.94)、(8.28±0.22)、(7.37±0.24)h;鞘内注射3种剂量后,表观分布容积(V1/F)分别为(2.58±0.42)、(2.35±0.9)、(5.13±0.63)L/kg,静脉给药3种剂量后,表观分布容积分别为(3.10±0.53)、(5.49±0.44)、(9.77±0.72)L/kg;鞘内注射3种剂量后,清除率(CL/F)分别为(0.04±0.02)、(0.08±0.01)、(0.18±0.04)L/(kg.h);静脉给药3种剂量后,清除率分别为(0.29±0.06)、(0.32±0.03)、(0.58±0.06)L/(kg.h);鞘内注射3种剂量后,曲线下面积(AUC(0-∞))分别为(9.24±0.81)、(9.8±0.69)、(10.98±0.23)mg/(L.h);静脉给药3种剂量后,曲线下面积(AUC(0-∞))分别为(1.26±0.34)、(2.21±0.19)、(2.42±0.25)mg/(L.h);鞘内给药后,心、肾、肺、脾、胃及脂肪等脑外组织药物含量2h达到峰浓度,肝、肠及肌肉组织8h药物浓度达高峰,静脉给药后,心、肝、肾、肺、脾、胃、肌肉及脂肪等脑外组织药物含量15min达到峰浓度,肠2h药物浓度达高峰,鞘内给药15min,脑组织中药物峰浓度是静脉给药的3倍。结论与静脉给药相比脑脊液中药物分布半衰期和消除半衰期延长,表观分布容积和清除率减小,曲线下面积增大;脑组织中药物峰浓度高。 Objective To study the pharmacokinetics of rabbits after intrathecal imipenem / cilastatin treatment. Methods Rabbits were anesthetized with 20.0% urethane auricle vein. The administration mode was intrathecal injection and intravenous injection. Each administration mode was divided into low (0.35mg / kg), moderate (0.7mg / kg) (1.4mg / kg) three dose groups, imipenem / cilastatin group after administration at 0,15,30 min, 1,2,4,8,12,24 h cerebrospinal fluid in cerebrospinal fluid and The distribution of imipenem / cilastatin in cerebrospinal fluid and tissues was determined by HPLC after 15min, 2,8h after administration of middle dose group. The pharmacokinetic parameters were analyzed by DAS software. Results After intrathecal injection of low, medium and high dose of imipenem / cilastatin, the half life (t1 / 2α) of cerebrospinal fluid was (27.56 ± 7.25), (27.22 ± 5.7), (28.08 ± 8.37 ), and the half-life (t1 / 2β) were (26.67 ± 3.58), (28.23 ± 9.23) and (29.94 ± 6.21) h, respectively. The half-lives of drug distribution in cerebrospinal fluid after intravenous administration were (6.88 ± 0.55 , (8.25 ± 0.24) and (7.34 ± 0.21) h, and the elimination half-lives were (6.96 ± 0.94), (8.28 ± 0.22) and (7.37 ± 0.24) h respectively after intrathecal injection of three doses And apparent volume of distribution (V1 / F) were (2.58 ± 0.42), (2.35 ± 0.9) and (5.13 ± 0.63) L / kg, respectively. (0.43 ± 0.44) and (9.77 ± 0.72) L / kg, respectively. After intrathecal injection of three doses, the clearance rates were (0.04 ± 0.02), (0.08 ± 0.01) and (0.84 ± 0.06), (0.32 ± 0.03) and (0.58 ± 0.06) L / (kg · h) respectively after intratracheal administration of three dosages; After three doses, the area under the curve (AUC (0-∞)) was (9.24 ± 0.81), (9.8 ± 0.69) and (10.98 ± 0.23) mg / (Lh) Under the area (AUC (0-∞) ) Were (1.26 ± 0.34), (2.21 ± 0.19) and (2.42 ± 0.25) mg / (Lh), respectively. After intrathecal administration, contents of extrahepatic tissue such as heart, kidney, lung, spleen, Reached the peak concentration, liver, intestine and muscle tissue 8h drug concentration peak, intravenous administration, heart, liver, kidney, lung, spleen, stomach, muscle and fat and other brain tissue drug concentration reached peak concentration 15min, Concentration reached its peak, intrathecal administration of 15min, brain tissue peak drug concentration is three times the intravenous administration. Conclusion Compared with intravenous administration, the half-life and elimination half-life of drug distribution in cerebrospinal fluid are prolonged, the apparent volume of distribution and clearance rate are reduced, and the area under the curve is increased. The peak concentration of drug in brain tissue is high.