甘露醇脱水作用的药动学结合药效学研究

 目的:对甘露醇脱水作用的药动学结合药效学进行研究。方法:6只家兔，5名颅内高压患者iv200 g·L^-1的甘露醇后测定血清甘露醇浓度及脑脊液压，并应用溶剂扩散理论对甘露醇血清浓度-脑压下降效应的定量关来进行了分析。结果:iv 200 g· L^-1的甘露醇0.4 g·kg^-1后病人的药动学参数:A=(2.12.0)mmol·L^-1,B=(1.20±0. 45 ) mmol · L，a=(0.22±0.29 ) min^-1，β =(0.009 0±0.002 9 ) min^-1;兔A=(58.0±15.4 ) mmol · L^-1，K=(0.014±0.005)min^-1。病人药效学参数:K_w= (0.079±0.043)min^-1, K_b = (0.012 9±0.006 4);兔K_w= (0.055±0.031)min^-1,K_b=0.003 6±0.000 5。结论:甘露醇降脑压的最大效应时间比血药浓度高峰时问滞后27.6 min(兔36.1 min)，效应时I司为105.4 min(兔112.5 min)。

Combined pharmacokinetic pharmacodynamic modeling of mannitol

OBJECTIVE: To study pharmacokinetics and pharmacodynamics of mannitol in animals and patients. METHODS: 6 rabbits and 5 patients with high intracranial pressure were treated with 200 g· L^-1 mannitol. The serum concentration of mannitol and the intracranial pressure were measured simultaneously. The diffusion theory was applied to analyze the relationship between the serum concentration of mannitol and the decrease of intracranial pressure. RESULTS: The pharmacokinetic parameters of patients after iv 200 g·L^-1mannita! were A=(2.1±2.0)mmol·L^-1，B=(1.2±0.45 ) mmol ·L^-1，a=(0.22±0.29) min^-1， β=(0.009±0.002 9)min^-12.rabbits: A=(58.0±15.4 ) mmol · L^-1，K=(0.014±0.005) min^-1.The pharmacodynamic parameters derived from pharmacokinetic-pharmacodynamic modeling with diffusion theory were K_w=(0.079±0.043) min¹，K_b=(0.012 9±0.006 4), rabbits K_w=(0.055±0.031) min^-1， K_b=0.003 6±0.000 5. CONCLUSION: The lagtime of maximum effect after maximum concentration was 27.6 min for patients and 36.1 min .for rabbits, the effect time was 105.4 min for patients and 112. 5 min for rabbits respectively. The diffusion theory can be applied to analyze the concentration-effect data of mannitol successfully.