Brown N, Ho D H, Fong K L, Bogerd L, Maksymiuk A, Bolivar R, Fainstein V, Bodey G P
Antimicrob Agents Chemother. 1983 Apr;23(4):603-9. doi: 10.1128/AAC.23.4.603.
Using a recently developed radioimmunoassay, we performed 15 vancomycin pharmacology studies in cancer patients with infections. Vancomycin (500 mg) was infused intravenously for 30 min every 6 h for up to 7 days. The plasma disappearance curve was biphasic, with an initial half-life of less than 30 min. The second half-life (t1/2 beta), not dose related, varied from 1.4 to 231 h among the patients. In six studies of patients with normal hepatic functions, the t1/2 beta was 2.6 h; the rate of total clearance was 162 ml/min. In contrast, nine studies of patients with impaired liver function had a much longer t1/2 beta (37 h) and a decrease in the rate of total clearance to 48 ml/min. These factors resulted in an increase in the value of area under the concentration-time curve from 59 to 3,434 micrograms X h/ml. These results have demonstrated the importance of the effects of liver function on vancomycin disposition. The vancomycin dose and schedule should be adjusted for patients with liver impairment.
我们使用最近开发的放射免疫分析法，对15例患有感染的癌症患者进行了万古霉素药理学研究。万古霉素（500毫克）每6小时静脉输注30分钟，持续7天。血浆消失曲线呈双相性，初始半衰期小于30分钟。第二个半衰期（t1/2β）与剂量无关，在患者中从1.4小时到231小时不等。在六项肝功能正常患者的研究中，t1/2β为2.6小时；总清除率为162毫升/分钟。相比之下，九项肝功能受损患者的研究中，t1/2β长得多（37小时），总清除率降至48毫升/分钟。这些因素导致浓度-时间曲线下面积值从59微克·小时/毫升增加到3434微克·小时/毫升。这些结果证明了肝功能对万古霉素处置影响的重要性。对于肝功能受损的患者，应调整万古霉素的剂量和给药方案。
