Sato Masaki, Chida Kingo, Suda Takafumi, Muramatsu Hideaki, Suzuki Yoshinari, Hashimoto Hisakuni, Gemma Hitoshi, Nakamura Hirotoshi
Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
J Infect Chemother. 2006 Aug;12(4):185-9. doi: 10.1007/s10156-006-0446-y.
Teicoplanin has a long serum half-life, and therefore it takes time to reach a steady-state concentration. An initial loading procedure has been recommended for teicoplanin to enable prompt reaching of the optimal serum trough level (10-15 microg/ml). However, the dose of teicoplanin that should be administered to patients with varying renal function levels remains inconclusive. In this study, we monitored the serum concentrations of teicoplanin in patients with methicillin-resistant Staphylococcus aureus (MRSA) pneumonia and compared different teicoplanin serum concentrations and their clinical efficacy, investigating the significance of the mean dose administered during the initial 3 days. The study included 48 patients with MRSA pneumonia. The peak and trough concentrations of teicoplanin were determined utilizing a fluorescence polarization immunoassay and a two-compartment Bayesian population model. Teicoplanin was given at a loading dose of 400 or 800 mg on the first day, followed by maintenance doses of 200 or 400 mg. The mean initial dose (MID) over the first 3 days was calculated as: (loading dose + dose on 2nd day + dose on 3rd day)/3. Patients with an MID of 266.7 mg or less (400 mg for loading, 200 mg over the 2nd and 3rd days) did not have a trough level that exceeded 10 microg/ml at the point before the injection on the 4th day. Even in patients with hemodialysis (HD), an MID of 266.7 mg was not enough to provide a trough level of 10 microg/ml. Patients with an MID than 533.3 mg had significantly elevated trough levels, showing better outcomes. A multiple regression formula for predicting trough level before the fourth day of administration is given as: 0.034 + 0.030 x (MID; mg) - 0.057 x creatinine clearance (Ccr; ml/min). These findings suggest that 800 mg as an initial dose, followed by 400 mg maintenance doses over the following 2 days, makes it possible to safely attain an optimal trough level, even in the patients with HD.
替考拉宁具有较长的血清半衰期,因此需要时间才能达到稳态浓度。已建议对替考拉宁采用初始负荷给药方案,以便迅速达到最佳血清谷浓度(10 - 15微克/毫升)。然而,对于不同肾功能水平的患者应给予的替考拉宁剂量仍无定论。在本研究中,我们监测了耐甲氧西林金黄色葡萄球菌(MRSA)肺炎患者的替考拉宁血清浓度,并比较了不同的替考拉宁血清浓度及其临床疗效,研究了初始3天内平均给药剂量的意义。该研究纳入了48例MRSA肺炎患者。利用荧光偏振免疫分析法和二室贝叶斯群体模型测定替考拉宁的峰浓度和谷浓度。替考拉宁在第一天给予400或800毫克的负荷剂量,随后给予200或400毫克的维持剂量。前3天的平均初始剂量(MID)计算为:(负荷剂量 + 第2天剂量 + 第3天剂量)/3。MID为266.7毫克或更低的患者(负荷剂量400毫克,第2天和第3天为200毫克)在第4天注射前的谷浓度未超过10微克/毫升。即使在血液透析(HD)患者中,266.7毫克的MID也不足以提供10微克/毫升的谷浓度。MID大于533.3毫克的患者谷浓度显著升高,显示出更好的结果。给药第四天前预测谷浓度的多元回归公式为:0.034 + 0.030×(MID;毫克) - 0.057×肌酐清除率(Ccr;毫升/分钟)。这些发现表明,800毫克作为初始剂量,随后在接下来的2天给予400毫克维持剂量,即使在HD患者中也能安全地达到最佳谷浓度。