EFFECTS OF AGE AND GENDER ON PHARMACOKINETICS OF CEFEPIME
EFFECTS OF AGE AND GENDER ON PHARMACOKINETICS OF CEFEPIME
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DOI：
10.1128/aac.36.6.1181
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发表时间：
1992-06-01
影响因子：
4.9
通讯作者：
PITTMAN, KA
中科院分区：
文献类型：
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作者：
BARBHAIYA, RH;KNUPP, CA;PITTMAN, KA
在 48 名志愿者单次静脉注射 1,000 mg 剂量后，研究了年龄和性别对头孢吡肟药代动力学的影响。根据年龄和性别，男性和女性受试者被分为四组，每组由 12 名受试者组成。年轻受试者年龄在20至40岁之间，老年受试者年龄在65至81岁之间。从每个受试者身上采集连续血液和尿液样本，并通过经过验证的高压液相色谱分析和紫外线检测来分析头孢吡肟。通过非房室方法计算关键药代动力学参数。消除半衰期（T1/2）、体重归一化全身清除率（CL(T)）、肾清除率（CL(R)）和稳态分布容积（V(SS)）不存在性别相关差异。 t1/2、CL(T)、CL(R) 和 V(SS) 参数具有统计学上显着的年龄相关效应。在不同的研究组中，V(SS) 范围为 0.21 至 0.24 升/千克。老年受试者的 V(SS) 值显着大于年轻受试者。老年受试者的头孢吡肟 t1/2（约 3 小时）明显长于年轻受试者（约 2.2 小时）。四个研究组的 CL(T) 和 CL(R) 平均值分别为 1.11 至 1.56 和 0.99 至 1.44 ml/min/kg。在老年受试者中，CL(T) 和 CL(R) 的估计值显着低于年轻受试者中观察到的值。线性回归显示头孢吡肟和肌酐的清除率值之间存在良好的相关性。头孢吡肟药代动力学与年龄相关的变化幅度不足以建议肾功能正常的老年患者调整剂量。
The effects of age and gender on the pharmacokinetics of cefepime were examined in 48 volunteers following administration of a single 1,000-mg intravenous dose. Male and female subjects were divided into four groups, each consisting of 12 subjects, according to their age and gender. The young subjects were between 20 and 40 years of age and elderly subjects were between 65 and 81 years of age. Serial blood and urine samples were collected from each subject and were analyzed for cefepime by validated high-pressure liquid chromatographic assays with UV detection. Key pharmacokinetic parameters were calculated by noncompartmental methods. There were no gender-related differences in elimination half-life (T1/2) and weight-normalized total body clearance (CL(T)), renal clearance (CL(R)), and steady-state volume of distribution (V(SS)). Statistically significant age-related effects were found for t1/2, CL(T), CL(R), and V(SS) parameters. In different study groups, V(SS), ranged from 0.21 to 0.24 liter/kg. The values for V(SS) were significant greater for elderly subjects than they were for young subjects. The cefepime t1/2 was significantly longer in elderly subjects (about 3 h) than that observed in young subjects (about 2.2 h). The mean values for CL(T), and CL(R) in the four study groups ranged from 1.11 to 1.56 and 0.99 to 1.44 ml/min/kg, respectively. In elderly subjects, the estimates for CL(T) and CL(R) were significantly lower than those observed in young subjects. Linear regression revealed good correlations between clearance values of cefepime and creatinine. The magnitude of age-related changes in the pharmacokinetics of cefepime is not significant enough to recommend dosage adjustment in elderly patients with kidney functions normal for their age.