Kozawa O, Uematsu T, Matsuno H, Niwa M, Takiguchi Y, Matsumoto S, Minamoto M, Niida Y, Yokokawa M, Nagashima S, Kanamaru M
Department of Pharmacology, Gifu University School of Medicine, Japan.
Antimicrob Agents Chemother. 1998 Jun;42(6):1433-6. doi: 10.1128/AAC.42.6.1433.
The pharmacokinetics and tolerability of a new parenteral carbapenem antibiotic, biapenem (L-627), were studied in healthy elderly volunteers aged 65 to 74 years (71.6 +/- 2.7 years [mean +/- standard deviation], n = 5; group B) and > or = 75 years (77.8 +/- 1.9 years, n = 5; group C), following single intravenous doses (300 and 600 mg), and compared with those of healthy young male volunteers aged 20 to 29 years (23.0 +/- 3.5 years, n = 5; group A). The agent was well tolerated in all three age groups. Serial blood and urine samples were analyzed for biapenem to obtain key pharmacokinetic parameters by both two-compartment model-dependent and -independent methods. The maximum plasma concentration and area under plasma concentration-versus-time curve (AUC) increased in proportion to the dose in all three groups. Statistically significant age-related effects for AUC, total body clearance, and renal clearance (CLR) were found, while elimination half-life (t1/2 beta) and percent cumulative recovery from urine of unchanged drug (% UR) remained unaltered (t1/2 beta, 1.51 +/- 0.42 [300 mg] and 2.19 +/- 0.64 [600 mg] h [group A], 1.82 +/- 1.14 and 1.45 +/- 0.36 h [group B], and 1.75 +/- 0.23 and 1.59 +/- 0.18 h [group C]; % UR, 52.6% +/- 3.0% [300 mg] and 53.1% +/- 5.1% [600 mg] [group A], 46.7% +/- 7.4% and 53.0% +/- 4.8% [group B], and 50.1% +/- 5.2% and 47.1% +/- 7.6% [group C]). A significant linear correlation was observed between the CLR of biapenem and creatinine clearance at the dose of 300 mg but not at 600 mg. The steady-state volume of distribution tended to be decreased with age, although not significantly. Therefore, the age-related changes in parameters of biapenem described above were attributable to the combination of decreased lean body mass and lowered renal function of the elderly subjects. However, the magnitude of those changes does not necessitate dosage adjustment in elderly patients with normal renal function for their age.
对一种新型肠外碳青霉烯类抗生素比阿培南（L - 627）的药代动力学和耐受性进行了研究。研究对象为65至74岁（平均年龄71.6±2.7岁[均值±标准差]，n = 5；B组）和≥75岁（平均年龄77.8±1.9岁，n = 5；C组）的健康老年志愿者，给予单次静脉注射剂量（300毫克和600毫克），并与20至29岁（平均年龄23.0±3.5岁，n = 5；A组）的健康年轻男性志愿者进行比较。该药物在所有三个年龄组中耐受性良好。通过两室模型依赖和非依赖方法分析系列血液和尿液样本中的比阿培南，以获得关键药代动力学参数。所有三组中，血浆最大浓度和血浆浓度 - 时间曲线下面积（AUC）均与剂量成比例增加。发现AUC、总体清除率和肾清除率（CLR）存在与年龄相关的统计学显著影响，而消除半衰期（t1/2β）和尿液中未变化药物的累积回收率（%UR）保持不变（t1/2β，A组：300毫克时为1.51±0.42小时，600毫克时为2.19±0.64小时；B组：1.82±1.14小时和1.45±0.36小时；C组：1.75±0.23小时和1.59±0.18小时；%UR，A组：300毫克时为52.6%±3.0%，600毫克时为53.1%±5.1%；B组：46.7%±7.4%和53.0%±4.8%；C组：50.1%±5.2%和47.1%±7.6%）。在300毫克剂量时观察到比阿培南的CLR与肌酐清除率之间存在显著线性相关性，但在600毫克剂量时未观察到。稳态分布容积虽有随年龄降低的趋势，但无显著差异。因此，上述比阿培南参数的年龄相关变化归因于老年受试者瘦体重减少和肾功能降低的综合作用。然而，对于肾功能正常的老年患者，这些变化的幅度并不一定需要根据其年龄调整剂量。
