Domart Y, Pierre C, Clair B, Garaud J J, Regnier B, Gibert C
Service de Réanimation Médicale, Hôpital Bichat, Paris, France.
Antimicrob Agents Chemother. 1987 Oct;31(10):1600-4. doi: 10.1128/AAC.31.10.1600.
The pharmacokinetics of teicoplanin were studied in 15 adult patients in the acute phase of severe infections caused by gram-positive cocci. All the subjects were given a daily intravenous bolus dose of 6 mg of teicoplanin kg-1 (body weight). The pharmacokinetic study was performed over a 48-h period after injection 4. The subjects were categorized according to their mean creatinine clearances (ml.min-1.kg-1) during the study period: group 1 (n = 3), greater than 1.6; group 2 (n = 6), 0.8 to 1.6; and group 3 (n = 6), 0.15 to 0.8. Mean concentrations of teicoplanin in serum at 1, 24, and 48 h were 33 +/- 8, 9 +/- 3, and 6 +/- 2.5 micrograms.ml-1, respectively. The mean half-lives of the concentration-time curve from 12 to 48 h were 28 +/- 4, 44 +/- 24, and 48 +/- 14 h in groups 1, 2, and 3, respectively (group 3 versus group 1: P less than 0.05). The mean area under the serum concentration-time curve from time zero to 24 h was 344 +/- 92 mg.h.liter-1, and the mean hybrid volume of distribution was 1.09 +/- 0.46 liter.kg-1. These values were similar for the three groups, with a trend for larger areas under the curve in group 3. Creatinine clearance correlated directly with the total body clearance of teicoplanin (r = 0.70) and with the renal clearance of teicoplanin (r = 0.82). However, in critically ill patients, the wide interindividual variations in pharmacokinetic parameters are more relevant than those related to the variations in renal function when creatinine clearance is above 0.30 ml.min-1.kg-1. We concluded that, in such conditions, monitoring of concentrations of teicoplanin in serum is mandatory.
对15例由革兰氏阳性球菌引起的严重感染急性期成年患者进行了替考拉宁的药代动力学研究。所有受试者均接受每日静脉推注剂量为6mg/kg(体重)的替考拉宁。在注射4后48小时内进行药代动力学研究。根据研究期间的平均肌酐清除率(ml.min-1.kg-1)对受试者进行分类:第1组(n = 3),大于1.6;第2组(n = 6),0.8至1.6;第3组(n = 6),0.15至0.8。替考拉宁在血清中1、24和48小时的平均浓度分别为33±8、9±3和6±2.5μg.ml-1。第1、2和3组中浓度-时间曲线从12至48小时的平均半衰期分别为28±4、44±24和48±14小时(第3组与第1组比较:P<0.05)。血清浓度-时间曲线从零至24小时的平均曲线下面积为344±92mg.h.liter-1,平均混合分布容积为1.09±0.46liter.kg-1。这三个组的这些值相似,第3组曲线下面积有增大趋势。肌酐清除率与替考拉宁的全身清除率直接相关(r = 0.70),与替考拉宁的肾清除率直接相关(r = 0.82)。然而,在危重症患者中,当肌酐清除率高于0.30ml.min-1.kg-1时,药代动力学参数的个体间广泛差异比与肾功能变化相关的差异更重要。我们得出结论,在这种情况下,必须监测血清中替考拉宁的浓度。