Pharmacokinetics of the Penicillins in Man
Pharmacokinetics of the Penicillins in Man
复制标题
青霉素在人体内的药代动力学
DOI：
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发表时间：
1976
影响因子：
4.5
通讯作者：
L. Weinstein
中科院分区：
文献类型：
--
作者：
M. Barza;L. Weinstein
摘要本文的目的是回顾和总结临床医生可能特别感兴趣的青霉素药代动力学行为的那些方面。虽然这些抗生素在酸稳定性和口服吸收方面存在显着差异，但通过简单检查口服给定剂量产生的最大血清浓度可能会得出误导性的推论。当考虑到血清蛋白结合和药物的内在活性时，就会出现更准确的情况。所有青霉素都很容易并由肾小管主动分泌，并且大多数在尿液中几乎完全没有变化地被消除。大多数青霉素在胆汁中少量排出，但这是从体内消除萘夫西林的主要途径。青霉素在“非专门”部位的分布非常好。相比之下，对中枢神经系统和眼睛的渗透性较差，对前列腺的渗透性也很小。炎症减少了渗透这些区域的障碍。然而，与人类这种现象相关的定量数据很少。丙磺舒积极与脑膜和肾小管细胞的“输出”泵竞争。这导致血液和脑脊液中青霉素浓度增加。该药剂对这些抗生素从眼睛和胆道主动分泌的影响很小。虽然青霉素从体内的消除主要通过肾脏排泄，但青霉素 V 和苯唑西林也被广泛降解。与“天然”和“广谱”青霉素的情况相反，异恶唑基同系物和萘夫西林的血清半衰期在肾功能衰竭的情况下仅略有延长。这些药物仅具有微弱的血液透析能力，而其他青霉素通过此过程可迅速从循环中去除。
SummaryThe purpose of this article is to review and summarise those aspects of the pharmacokinetic behaviour of the penicillins that may be of particular interest to the clinician.While these antibiotics differ markedly in their acid stability and oral absorption, misleading inferences may be drawn from simple inspection of the maximal serum concentrations produced by a given dose administered orally. A more accurate picture emerges when serum protein binding and intrinsic activity of the drugs are taken into account. All of the penicillins are readily and actively secreted by the renal tubules and most are eliminated, almost completely unchanged, in the urine. The majority are excreted in small quantities in the bile, but this is a major route for elimination of nafcillin from the body.Distribution of the penicillins in ‘non-specialised’ sites is excellent. In contrast, penetration of the central nervous system and eye are poor, and of the prostate, minimal. Inflammation reduces the barriers to penetration of these areas. However, quantitative data related to this phenomenon in man are few. Probenecid actively competes with the ‘export’ pump of the meninges and renal tubular cells. This results in an increase in concentrations of the penicillins in the blood and cerebrospinal fluid. The effect of this agent on active secretion of these antibiotics from the eye and biliary tract is minimal.While elimination of the penicillins from the body takes place largely via renal excretion, penicillin V and oxacillin are extensively degraded as well. In contrast to the situation with respect to ‘natural’ and ‘broad-spectrum’ penicillins, the serum half-life of the isoxazolyl congeners and nafcillin is only minimally prolonged in the presence of renal failure. These agents are only weakly haemodialyzable, while the other penicillins are rapidly removed from the circulation by this procedure.