Yee G C, Lennon T P, Gmur D J, Kennedy M S, Deeg H J
Clin Pharmacol Ther. 1986 Oct;40(4):438-43. doi: 10.1038/clpt.1986.204.
We evaluated the effect of age on cyclosporine pharmacokinetics in 69 nonobese patients aged 10 months to 56 years (median 22 years) undergoing allogeneic bone marrow transplantation for treatment of aplastic anemia or hematologic malignancy. Cyclosporine pharmacokinetics were studied during the first 2 posttransplant weeks after an intravenous dose of 2.6 to 3.5 mg/kg. Serum cyclosporine concentrations were measured by HPLC. Cyclosporine concentration-time data were fitted to a two-compartment model with a nonlinear regression program. There was a significant inverse linear correlation between age and both total systemic clearance (CL) (r = 0.42; P less than 0.001) and volume of distribution at steady-state (Vss) (r = 0.33; P less than 0.01). Mean (+/- SE) cyclosporine CL was 82 +/- 21, 45 +/- 5, 38 +/- 9, 44 +/- 8, and 20 +/- 3 ml/min/kg and mean cyclosporine Vss was 34 +/- 11, 28 +/- 10, 15 +/- 4, 14 +/- 5, and 4.7 +/- 0.7 L/kg in patients 0 to 10 (n = 12), 11 to 20 (n = 19), 21 to 30 (n = 12), 31 to 40 (n = 17), and greater than 40 (n = 9) years old, respectively. Patients 0 to 10 years old had a significantly higher cyclosporine CL than those 11 to 40 or greater than 40 years old and also had a significantly larger Vss than those greater than 40 yrs old (P less than 0.05). Age-related differences in CL or Vss were also observed when these parameters were normalized by body surface area.(ABSTRACT TRUNCATED AT 250 WORDS)
我们评估了年龄对69例非肥胖患者环孢素药代动力学的影响，这些患者年龄在10个月至56岁（中位数22岁）之间，因再生障碍性贫血或血液系统恶性肿瘤接受异基因骨髓移植。在静脉注射2.6至3.5mg/kg后的移植后前两周内研究环孢素药代动力学。血清环孢素浓度通过高效液相色谱法测定。环孢素浓度-时间数据用非线性回归程序拟合到二室模型。年龄与总全身清除率（CL）（r = 0.42；P<0.001）和稳态分布容积（Vss）（r = 0.33；P<0.01）之间均存在显著的负线性相关性。0至10岁（n = 12）、11至20岁（n = 19）、21至30岁（n = 12）、31至40岁（n = 17）和大于40岁（n = 9）患者的平均（±SE）环孢素CL分别为82±21、45±5、38±9、44±8和20±3ml/min/kg，平均环孢素Vss分别为34±11、28±10、15±4、14±5和4.7±0.7L/kg。0至10岁患者的环孢素CL显著高于11至40岁或大于40岁的患者，且Vss也显著大于大于40岁的患者（P<0.05）。当这些参数按体表面积标准化时，也观察到CL或Vss的年龄相关差异。（摘要截断于250字）
