Pharmacokinetics of new broad-spectrum cephamycin, YM09330, parenterally administered to various experimental animals
Pharmacokinetics of new broad-spectrum cephamycin, YM09330, parenterally administered to various experimental animals
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新型广谱头霉素YM09330对各种实验动物胃肠外给药的药代动力学
DOI：
10.1128/aac.20.2.176
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发表时间：
1981
影响因子：
4.9
通讯作者：
K. Yano
中科院分区：
文献类型：
--
作者：
M. Komiya;Y. Kikuchi;A. Tachibana;K. Yano
研究了新型半合成头孢霉素YM09330在实验动物体内经静脉和肌肉给药后的药代动力学。静脉给药20mg /kg后30min， YM09330的平均血浆水平为小鼠5.5微克/ml，大鼠17微克/ml，家兔24微克/ml，狗42微克/ml，猴子76微克/ml；血浆半衰期分别为13.0、15.9、30.5、55.5和75.6分钟。YM09330的半衰期均比头孢美唑长。在猴子中，YM09330的血浆水平比头孢唑林更高，持续时间更长。在大鼠和狗的肾脏中，YM09330的浓度最高，依次为肝脏、血浆、肺、脾和心脏；它们与头孢唑林对大鼠的影响相似。静脉给药后48小时内，YM09330的尿排泄量为小鼠的67%，大鼠的52%，家兔的74%，狗的53%，猴子的60%。在大鼠中，48%剂量的YM09330在血浆、尿液或胆汁中检测到。然而，在小鼠、大鼠和狗的尿液中发现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发现了大量的互变异构体。大鼠血清蛋白结合率为30%，家兔为51%，犬为39%，猴为87%，人为91%。
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.