Komiya M, Kikuchi Y, Tachibana A, Yano K
Antimicrob Agents Chemother. 1981 Aug;20(2):176-83. doi: 10.1128/AAC.20.2.176.
The pharmacokinetics of YM09330, a new semisynthetic cephamycin, were determined after intravenous and intramuscular administration to experimental animals. Mean plasma levels of YM09330 at 30 min after intravenous administration of 20 mg/kg were 5.5 micrograms/ml for mice, 17 micrograms/ml for rats, 24 micrograms/ml for rabbits, 42 micrograms/ml for dogs, and 76 micrograms/ml for monkeys; plasma half-lives were 13.0, 15.9, 30.5, 55.5, and 75.6 min, respectively. The half-lives of YM09330 were longer than those of cefmetazole in all species tested. In monkeys, plasma levels of YM09330 were higher and more prolonged than those of cefazolin. In rats and dogs, the concentrations of YM09330 were highest in the kidneys, followed by the liver, plasma, lung, spleen, and heart in that order; they were similar to those of cefazolin in rats. Urinary excretion of YM09330 within 48 h of intravenous administrations was 67% of the dose in mice, 52% in rats, 74% in rabbits, 53% in dogs, and 60% in monkeys. In rats, 48% of the dose of YM09330 was detected in the plasma, urine, or bile. However, small amounts of an antibacterially active tautomer of YM09330 were recovered in the urine of mice, rats, and dogs, whereas large amounts of the tautomer were recovered in the urine of rabbits and monkeys. Serum protein binding of YM09330 was 30% of rats, 51% for rabbits, 39% for dogs, 87% for monkeys, and 91% for humans.
新型半合成头孢霉素YM09330在对实验动物进行静脉注射和肌肉注射后，测定了其药代动力学。静脉注射20mg/kg后30分钟，小鼠体内YM09330的平均血浆水平为5.5微克/毫升，大鼠为17微克/毫升，兔子为24微克/毫升，狗为42微克/毫升，猴子为76微克/毫升；血浆半衰期分别为13.0、15.9、30.5、55.5和75.6分钟。在所有测试物种中，YM09330的半衰期均长于头孢美唑。在猴子中，YM09330的血浆水平高于头孢唑林，且持续时间更长。在大鼠和狗中，YM09330在肾脏中的浓度最高，其次依次为肝脏、血浆、肺、脾脏和心脏；在大鼠中，其浓度与头孢唑林相似。静脉注射后48小时内，YM09330在小鼠、大鼠、兔子、狗和猴子尿液中的排泄量分别为给药剂量的67%、52%、74%、53%和60%。在大鼠中，给药剂量的48%可在血浆、尿液或胆汁中检测到。然而，在小鼠、大鼠和狗的尿液中仅回收了少量具有抗菌活性的YM09330互变异构体，而在兔子和猴子的尿液中回收了大量该互变异构体。YM09330与血清蛋白的结合率在大鼠中为30%，兔子中为51%，狗中为39%，猴子中为87%，人类中为91%。
