Arancibia A, Baillarie D, Bravo M, Chávez J
Department of Technological and Pharmaceutical Sciences, University of Chile, Santiago.
Int J Clin Pharmacol Ther. 1995 Nov;33(11):623-7.
Dibekacin pharmacokinetics was studied in 3 healthy volunteers, 5 patients with renal failure presenting Clcr, between 4.0 and 67 ml min-1 per 1.73 m2 of body surface and 5 anephric patients given as a 30 minute intravenous infusion. The antibiotic was assayed in plasma and urine by means of a high performance liquid chromatography (HPLC) method. A two compartment kinetic model was used to describe the bi-phasic decline of plasma concentration and to calculate the different pharmacokinetic parameters. Slow disposition and elimination rate constants beta and k10 respectively, and total body clearance were markedly diminished in anephric patients (p << 0.001): t1/2 beta = 2.12 h, k10 = 0.642 h-1 and Cl = 0.882 ml/min per kg, in normal subjects and t1/2 beta = 4.73 h, k10 = 0.278 h-1 and Cl = 0.693 ml/min per kg in anephric patients. The apparent volumes of distribution increased while the creatinine clearance of the patients decreased. Thus Vd(area) of volunteers with normal renal function was statistically significantly lower than that of anephric patients (p < 0.001), from a value of 0.162 to 0.281 l/kg respectively. A good correlation (r = 0.982) between patient's slow disposition constant beta and creatine clearance was found. Urinary recovery at 24 h was 85.6% of the dose given to normal volunteers. This value decreased while impairment increased. The mean extraction coefficient, during hemodialysis was about 0.35.
对3名健康志愿者、5名肌酐清除率（Clcr）在每1.73平方米体表面积4.0至67毫升/分钟之间的肾衰竭患者以及5名无肾患者进行了30分钟静脉输注的地贝卡星药代动力学研究。采用高效液相色谱（HPLC）法测定血浆和尿液中的抗生素。使用二室动力学模型描述血浆浓度的双相下降，并计算不同的药代动力学参数。无肾患者的慢处置率常数β和消除率常数k10以及总体清除率明显降低（p << 0.001）：正常受试者中t1/2β = 2.12小时，k10 = 0.642小时-1，Cl = 0.882毫升/分钟/千克，无肾患者中t1/2β = 4.73小时，k10 = 0.278小时-1，Cl = 0.693毫升/分钟/千克。随着患者肌酐清除率的降低，表观分布容积增加。因此，肾功能正常的志愿者的Vd(area)在统计学上显著低于无肾患者（p < 0.001），分别为0.162至0.281升/千克。发现患者的慢处置常数β与肌酐清除率之间具有良好的相关性（r = 0.982）。给予正常志愿者的剂量在24小时的尿回收率为85.6%。随着肾功能损害增加，该值降低。血液透析期间的平均提取系数约为0.35。
