Komiya I, Murata S, Umemura K, Tomono N, Kikai S, Fujita M
J Pharmacobiodyn. 1981 May;4(5):356-61. doi: 10.1248/bpb1978.4.356.
The LD50 values of dibekacin to mice were determined following three different methods of administration, namely, intravenous constant infusion, intravenous bolus injection, and intramuscular injection. The serum levels of dibekacin were pharmacokinetically analyzed. The differences in LD50 values between the methods of administration were discussed from the viewpoints of pharmacokinetics. 1) The LD50 value following the intravenous constant infusion was higher than that following the intravenous bolus injection and approached the level of that following the intramuscular injection, when the infusion rate of the drug was decreased by increasing the infusion period. 2) The biological half-life of dibekacin in mice was 24--45 min. 3) The volume of distribution increased as its dose increased, and a linear correlation was noted between log Vd and log (dose). 4) The difference among the maximum serum concentrations calculated with dibekacin following the administration of LD50 was small, which coincided with the results of the experiment that the serum concentrations of dibekacin at the death following the administration of LD100 were almost the same regardless of the method of administration.
采用三种不同给药方法，即静脉恒速输注、静脉推注和肌肉注射，测定了双去甲庆大霉素对小鼠的半数致死量（LD50）。对双去甲庆大霉素的血清水平进行了药代动力学分析。从药代动力学角度讨论了不同给药方法之间LD50值的差异。1）当通过延长输注时间降低药物输注速率时，静脉恒速输注后的LD50值高于静脉推注后的LD50值，且接近肌肉注射后的水平。2）双去甲庆大霉素在小鼠体内的生物半衰期为24 - 45分钟。3）分布容积随剂量增加而增大，log Vd与log（剂量）之间呈线性相关。4）给予LD50后计算得到的最大血清浓度之间差异较小，这与给予LD100后无论给药方法如何，死亡时双去甲庆大霉素的血清浓度几乎相同的实验结果一致。
