Hirata C A, Guay D R, Awni W M, Stein D J, Peterson P K
Drug Evaluation Unit, Hennepin County Medical Center, Minneapolis, Minnesota 55415.
Antimicrob Agents Chemother. 1989 Nov;33(11):1927-31. doi: 10.1128/AAC.33.11.1927.
The steady-state pharmacokinetics of ciprofloxacin were evaluated in nine elderly patients with lower respiratory tract infections after an intravenous dosage regimen of 200 mg every 12 h (n = 9) and an oral dosage regimen of 750 mg every 12 h (n = 6). Ciprofloxacin concentrations in serum and urine were measured by high-performance liquid chromatography. The peak concentration in serum, total body clearance (CLs), steady-state volume of distribution (Vss), and terminal elimination half-life after intravenous dosing were 3.5 +/- 0.8 micrograms/ml, 4.38 +/- 1.80 ml/min per kg, 1.6 +/- 0.6 liters/kg, and 5.8 +/- 2.4 h, respectively. The peak concentration in serum, time to peak concentration in serum, absorption lag time, and absolute bioavailability (F) after oral dosing were 7.6 +/- 2.2 micrograms/ml, 1.9 +/- 1.0 h, 0.4 +/- 0.5 h, and 7.7 +/- 24.2%, respectively. The elevated drug concentrations in serum samples from the elderly after oral dosing, compared with data obtained from younger subjects, appear to be a function of reduced CLs, renal clearance, and Vss. The increased F observed in some patients may be due to the effect of concomitant or proximate administration of tube feedings, medications which may alter gastric motility or acidity, or decreased first-pass metabolism. The results demonstrate that factors related to age and declining renal function, rather than infectious disease state, may be primary in determining alterations in pharmacokinetic parameters in the elderly. In elderly patients with normal renal function for their age, no dosage adjustment for intravenous or oral ciprofloxacin is necessary.
对9名患有下呼吸道感染的老年患者进行了环丙沙星的稳态药代动力学评估，静脉给药方案为每12小时200mg（n = 9），口服给药方案为每12小时750mg（n = 6）。采用高效液相色谱法测定血清和尿液中环丙沙星的浓度。静脉给药后血清中的峰值浓度、总体清除率（CLs）、稳态分布容积（Vss）和末端消除半衰期分别为3.5±0.8μg/ml、4.38±1.80ml/min per kg、1.6±0.6升/kg和5.8±2.4小时。口服给药后血清中的峰值浓度、血清达峰时间、吸收滞后时间和绝对生物利用度（F）分别为7.6±2.2μg/ml、1.9±1.0小时、0.4±0.5小时和7.7±24.2%。与年轻受试者的数据相比，老年患者口服给药后血清样本中药物浓度升高似乎是CLs、肾清除率和Vss降低的结果。在一些患者中观察到的F增加可能是由于同时或接近给予管饲、可能改变胃动力或酸度的药物的影响，或首过代谢降低。结果表明，与年龄和肾功能下降相关的因素，而非感染性疾病状态，可能是决定老年患者药代动力学参数改变的主要因素。对于年龄相符且肾功能正常的老年患者，静脉或口服环丙沙星无需调整剂量。
