Matzke G R, Zhanel G G, Guay D R
Clin Pharmacokinet. 1986 Jul-Aug;11(4):257-82. doi: 10.2165/00003088-198611040-00001.
Vancomycin utilisation has increased dramatically in the last 10 years due to the increasing clinical significance of infections with methicillin-resistant staphylococci. Recent studies have focused on characterising the disposition of vancomycin in patients and assessing the relationship between serum concentrations and therapeutic as well as adverse effects. Although vancomycin is not appreciably absorbed from the intact gastrointestinal tract, several recent case reports have documented the attainment of therapeutic and potentially toxic vancomycin serum concentrations following oral administration to patients with pseudomembranous colitis. The disposition of parenterally administered vancomycin has been best characterised by a triexponential model. The half-life of the initial phase (t1/2 pi) is approximately 7 minutes, that of the second phase (t1/2 alpha) is approximately 0.5 to 1 hour, while the terminal elimination half-life (t1/2 beta) ranges from 3 to 9 hours in subjects with normal renal function. The volume of the central compartment (Vc) in adults is approximately 0.15 L/kg while the steady-state volume of distribution (Vdss) ranges from 0.39 to 0.97 L/kg. More than 80% of a vancomycin dose is excreted unchanged in the urine within 24 hours after administration, and the concentration of vancomycin in liver tissue and bile has been reported to be at or below detection limits. Vancomycin renal clearance approximates 0.5 to 0.8 of simultaneously determined creatinine or 125I-iothalamate clearances, suggesting that the primary route of renal excretion is glomerular filtration. Recently, non-renal factors such as hepatic conjugation have been proposed as an important route of vancomycin elimination. However, these data are difficult to reconcile with other studies showing minimal non-renal clearance of vancomycin in subjects with end-stage renal disease. As yet, the disposition of vancomycin in patients with hepatic disease has not been adequately defined. Only limited data are available regarding the concentrations of vancomycin in biological fluids other than plasma. The penetration of vancomycin into cerebrospinal fluid (CSF) in patients with and without meningitis has been quite variable. Although early studies suggested that adequate CSF concentrations may not be achieved in subjects with uninflamed meninges, more recent investigations have reported contradictory results. Therapeutic concentrations of vancomycin, i.e. greater than 2.5 mg/L, have, however, been reported in ascitic, pericardial, pleural and synovial fluids. Tissue concentrations of vancomycin have exceeded simultaneous serum concentrations in heart, kidney, liver and lung sp
在过去10年中，由于耐甲氧西林葡萄球菌感染的临床重要性不断增加，万古霉素的使用量急剧上升。最近的研究集中在描述万古霉素在患者体内的处置情况，并评估血清浓度与治疗效果及不良反应之间的关系。尽管万古霉素在完整的胃肠道中吸收不明显，但最近有几例病例报告记录了伪膜性结肠炎患者口服万古霉素后达到了治疗性和潜在毒性的血清浓度。静脉注射万古霉素的处置情况最好用三指数模型来描述。初始阶段的半衰期（t1/2π）约为7分钟，第二阶段的半衰期（t1/2α）约为0.5至1小时，而在肾功能正常的受试者中，终末消除半衰期（t1/2β）为3至9小时。成人中央室的容积（Vc）约为0.15L/kg，而稳态分布容积（Vdss）为0.39至0.97L/kg。超过80%的万古霉素剂量在给药后24小时内以原形经尿液排出，据报道肝组织和胆汁中万古霉素的浓度处于或低于检测限。万古霉素的肾清除率约为同时测定的肌酐清除率或125I-碘他拉酸盐清除率的0.5至0.8，这表明肾排泄的主要途径是肾小球滤过。最近，肝结合等非肾因素被认为是万古霉素消除的重要途径。然而，这些数据很难与其他研究结果相协调，其他研究表明终末期肾病患者的万古霉素非肾清除率极低。到目前为止，万古霉素在肝病患者中的处置情况尚未得到充分界定。关于血浆以外生物体液中万古霉素浓度的数据有限。万古霉素在有和没有脑膜炎的患者中进入脑脊液（CSF）的情况差异很大。尽管早期研究表明在未发炎的脑膜患者中可能无法达到足够的脑脊液浓度，但最近的研究报告了相互矛盾的结果。然而，在腹水、心包积液、胸腔积液和滑液中已报告了治疗浓度的万古霉素，即大于2.5mg/L。万古霉素在心脏、肾脏、肝脏和肺组织中的浓度超过了同时期的血清浓度。
