临床药物动力学的新抗菌4-quinolones。
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纽曼米
临床药物动力学的新抗菌4-quinolones。
Pharmacokinet。1988年2月,14 (2):96 - 121。
- PubMed ID
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3282749 (在PubMed]
- 文摘
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结构修改所谓的“第一代”或“尿”喹诺酮导致大量增加其内在抗菌活性,与药代动力学性质的变化。组织渗透是最引人注目的变化,新喹诺酮类与新广谱beta-lactams可比临床表现的活动。销售化合物4-quinolones组包括pefloxacin,氧氟沙星,enoxacin,环丙沙星和诺氟沙星;更多的化合物在不同阶段的研究和发展。必威国际app4-quinolones法案通过抑制细菌的DNA促旋酶,pH值和浓度依赖的一个过程。杀菌活动可以部分废除如果抑制蛋白质合成氯霉素,或者如果RNA合成抑制了利福平(利福平)。活动包括甲氧西林的抗菌谱,gentamicin-resistant葡萄球菌抗多种抗菌素的non-fermenters,肠杆菌科,军团菌、奈瑟氏菌属的物种,布兰汉氏球菌属和流感嗜血杆菌。除了诺氟沙星,只有30 - 40%生物从口腔路线,可利用4-quinolones 80到100%,吸收发生在1到3个小时。食品不显著改变Cmax, AUC或者消除半衰期,尽管达峰时间,可能会增加。4-quinolones广泛分布到全身,分布容积大于1.5 L /公斤。 Protein binding is less than 30% in most cases. Penetration into most tissues is good. With the exception of ofloxacin and lomefloxacin (NY 198), which are metabolically stable, metabolism of the 4-quinolones occurs primarily at the C7 position in the piperazinyl ring. Biotransformation is extensive (85%) with pefloxacin, medium (25 to 40%) with ciprofloxacin and enoxacin, and low (less than 20%) with norfloxacin. Elimination half-lives vary between 3 and 5 hours (ciprofloxacin) and 8 to 14 hours (pefloxacin). Biliary concentrations of the 4-quinolones are 2 to 10 times greater than those in serum or plasma, with several compounds undergoing enterohepatic circulation. There is some evidence that ciprofloxacin, norfloxacin, ofloxacin and enoxacin have an active renal tubular excretion pathway. In impaired renal function, reduction of the glomerular filtration rate below 30 ml/min (1.8 L/h) is associated with an increase in elimination half-life and AUC, and a decrease in renal and total clearance of the 4-quinolones, and a decrease in 24-hour urinary recovery.(ABSTRACT TRUNCATED AT 400 WORDS)