Kita Y, Yamazaki T, Imada A
Biology Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
Antimicrob Agents Chemother. 1992 Nov;36(11):2481-6. doi: 10.1128/AAC.36.11.2481.
The pharmacokinetic properties of SCE-2787 administered intravenously at a dose of 20 mg/kg of body weight were studied with mice, rats, rabbits, dogs, and monkeys and were compared with those of ceftazidime, cefpirome, and cefclidin in mice and dogs. The area under the concentration-time curve for plasma after intravenous administration was the largest in monkeys, followed by those in dogs, rabbits, rats, and mice, in that order. The elimination half-life ranged from 0.2 to 0.3 h in mice and rats to 0.7 to 1.3 h in rabbits, dogs, and monkeys. In young dogs, the concentrations of SCE-2787 in plasma were somewhat lower than those in the mature dogs. SCE-2787 was distributed well to the tissues, and the highest concentration was found in the kidneys in all species tested; the distribution to the lungs, liver, and spleen was also good, but the concentrations in these tissues were lower than those in the plasma. The pharmacokinetic parameters and urinary excretion of SCE-2787 in mice and dogs were similar to those of ceftazidime, cefpirome, and cefclidin. The maximum concentrations in the cerebrospinal fluid of rats and rabbits were 0.8 and 1.3 micrograms/ml, and the relative percentages of the area under the concentration-time curve of SCE-2787 in the cerebrospinal fluid to that in the plasma were 4.6 and 6.4%, respectively. SCE-2787 was excreted mainly in the urine; the recovery rate ranged from 74% (rats) to 90% (dogs) of the dose. The biliary excretion of SCE-2787, however, was low, amounting to about 1.4% for mice and rats and less than 0.5% for rabbits and dogs. In rats, there was no accumulation in the tissues and no delay in urinary excretion upon multiple intravenous administration of 20 mg of SCE-2787 per kg once daily for 7 days. No active metabolites were found in the plasma or urine of animals given SCE-2787. The binding of SCE-2787 to serum protein in mice, rats, dogs, monkeys, and humans was less than 11% and similar to that of cefclidin.
以20mg/kg体重静脉注射SCE - 2787后，对小鼠、大鼠、兔子、狗和猴子的药代动力学特性进行了研究，并与头孢他啶、头孢匹罗和头孢利定在小鼠和狗体内的药代动力学特性进行了比较。静脉给药后，血浆浓度 - 时间曲线下面积在猴子中最大，其次是狗、兔子、大鼠和小鼠，顺序依次为上述顺序。消除半衰期在小鼠和大鼠中为0.2至0.3小时，在兔子、狗和猴子中为0.7至1.3小时。在幼犬中，血浆中SCE - 2787的浓度略低于成年犬。SCE - 2787在组织中分布良好，在所有受试物种的肾脏中浓度最高；在肺、肝和脾中的分布也良好，但这些组织中的浓度低于血浆中的浓度。SCE - 2787在小鼠和狗体内的药代动力学参数和尿排泄情况与头孢他啶、头孢匹罗和头孢利定相似。大鼠和兔子脑脊液中的最大浓度分别为0.8和1.3微克/毫升，SCE - 2787在脑脊液中浓度 - 时间曲线下面积与血浆中该曲线下面积的相对百分比分别为4.6%和6.4%。SCE - 2787主要经尿液排泄；回收率在剂量的74%（大鼠）至90%（狗）之间。然而，SCE - 2787的胆汁排泄量较低，小鼠和大鼠约为1.4%，兔子和狗低于0.5%。在大鼠中，每天一次以20mg/kg的剂量静脉注射SCE - 2787，连续7天，组织中无蓄积，尿排泄无延迟。在给予SCE - 2787的动物血浆或尿液中未发现活性代谢物。SCE - 2787与小鼠、大鼠、狗、猴子和人类血清蛋白的结合率小于11%，与头孢利定相似。
