The Animal Experiment Study Of Pharmacokinetics And Pharmacodynamics Changes Of Cisatracurium In Different Doses Under Three Level Of Body Temperature

Objective To compare the pharmacokinetics and pharmacodynamics of cisatracurium with three level of body temperature in rabbits under different doses.Methods 72 healthy rabbits weighing 2.0～2.3 kg were used in the study. They were randomly allocated to normothermia group(group C), hyperthermia group (group H) and hypothermia group(group L), NBT=24. The separate rectal temperature of group C, group H and group L were 38.5, 41.8 and 34.5°C. Each group was also allocated to groupⅠ,Ⅱ,ⅢandⅣrandomly, Ndose=6.The Separate dose of injection inⅠ～Ⅳgroups were 0.33, 0.66, 0.99 and 1.32 mg·kg-1 cisatracurium. Blood samples were taken from jugular vein at 2, 4, 6, 8, 10, 12, 15, 30, 60, 90 and 120 min after injection.The plasma concentration of cisatracurium was detected by high performance liquid chromatography (HPLE). Elimination half life(t1/2β) and elimination rate constant(kβ) were calculated by 3p97 pharmacokinetics software. MAP, HR and rectum temperature were recorded immediately 5 min before modeling, 2 min before administration, at 4, 10, 30, 60 and 90 min after administration. Onset time, recovery index, clinical duration time were measured.Results The t1/2βand plasma durg concentration were significantly increased in group L and were significantly decreased in group H(P <0.05). The kβwas significantly decreased in group L and was significantly increased in group H(P<0.01). The t1/2βand kβwere not significantly distinct among different doses. With the elevation of initial doses of rabbits, plasma durg concentration was increased(P<0.05). The onset time, recovery index and clinical duration time were significantly increased in group L and were significantly increased in group H(P <0.05). With the elevation of initial doses of rabbits, onset time of cisatracurium was cut down(P <0.01), clinical duration time was extended(P <0.01).The recovery index of different doses was not significantly distinct among different doses. Compared with pro-modeling, MAP was significantly increased in group L and was decreased in group H(P <0.05), but the HR was significantly increased in both group H and group L(P <0.05).Conclusion The degradation rate and neuromuscular block effect of cisatracurium in rabbit are changed by body temperature. With the elevation of temperature of the rabbits, the degradation rate of cisatracurium is speeded up, while the neuromuscular block effect of cisatracurium is cut down. The elimination rate is not significantly distinct at doses range from 0.33 to 1.32mg·kg-1. The neuromuscular block effect of cisatracurium is offered to be dose dependent. With the elevation of initial doses of rabbits, the neuromuscular block effect of cisatracurium is enhanced, effect of hump crest is not inspected.