Bunchman T E, Parekh R S, Flynn J T, Smoyer W E, Kershaw D B, Valentini R P, Pontillo B J, Sandvordenker J, Brown C, Sedman A B
Division of Pediatric Nephrology, University of Michigan, Ann Arbor 48109, USA.
Pediatr Nephrol. 1998 Jan;12(1):2-5. doi: 10.1007/s004670050390.
Neoral was instituted in pediatric renal transplant patients with the hypothesis it would have more predictable kinetics than Sandimmun. However, significant questions have arisen concerning potential toxicity and dosing interval related to its rapid absorption with subsequent high initial peak. This is compounded by the fact that children appear to metabolize cyclosporine at a greater rate than adults. This combination of a rapid peak and rapid absorption may then result in lower trough levels at 12 h. We compared the trough cyclosporine levels of nine children who received Neoral with nine who received Sandimmun at the time of initial transplantation. More frequent dosing (every 8 h) was required in the Neoral population compared with the Sandimmun population for the 1st month in order to obtain comparable trough levels. Beyond the initial 4-6 weeks, trough levels were similar for Neoral and Sandimmun. Whereas 1-month creatinine levels and blood pressures were similar, the number of blood pressure medications was significantly higher in the Neoral group. At 5.5 +/- 1.1 months' followup, a single patient in the current Neoral group and in the retrospective Sandimmun group each experienced a single OKT3 allograft-treated rejection. We suggest that the area under the curve is different in Neoral than Sandimmun, and the initial dosing frequency may need to be adjusted accordingly.
对小儿肾移植患者使用新山地明,基于的假设是其药代动力学比山地明更具可预测性。然而,关于其快速吸收及随后的高初始峰浓度所带来的潜在毒性和给药间隔,出现了重大问题。儿童似乎比成人以更快的速度代谢环孢素,这一事实使情况更加复杂。快速的峰浓度和快速吸收相结合,可能会导致12小时时的谷浓度较低。我们比较了9名在初次移植时接受新山地明的儿童与9名接受山地明的儿童的环孢素谷浓度。在第1个月,与接受山地明的人群相比,接受新山地明的人群需要更频繁地给药(每8小时一次),以获得可比的谷浓度。在最初的4 - 6周之后,新山地明和山地明的谷浓度相似。虽然1个月时的肌酐水平和血压相似,但新山地明组的降压药物数量明显更高。在5.5±1.1个月的随访中,当前接受新山地明治疗的组和回顾性接受山地明治疗的组各有1例患者经历了1次OKT3治疗的移植排斥反应。我们认为新山地明的曲线下面积与山地明不同,初始给药频率可能需要相应调整。