Dunn S, Cooney G, Sommerauer J, Lindsay C, McDiarmid S, Wong R L, Chang C T, Smith H T, Choc M G
Department of Surgery, St. Christopher's Hospital for Children, Temple University School of Medicine, Philadelphia, Pennsylvania 19134, USA.
Transplantation. 1997 Jun 27;63(12):1762-7. doi: 10.1097/00007890-199706270-00010.
A comparison of the oral bioavailability of cyclosporine from the original formulation (CsA) and from the new formulation, cyclosporine for microemulsion (CsA-ME), was made in pediatric maintenance liver transplant patients within two age groups (group 1, ages 1-5 years; group 2, ages 6-17 years) in an open-label, multicenter, randomized crossover trial. All patients were at least 6 months past transplantation and were receiving CsA maintenance therapy.
In study period 1 (days 1 through 14), patients were administered either CsA or CsA-ME at the same b.i.d. dosage as their maintenance therapy. Upon entry into period 2 (days 15 through 28), patients were converted to the alternate formulation at a 1:1 mg dose ratio. On day 29, all patients returned to the CsA treatment administered at study entry, with follow-up on day 35. Dosage adjustments were not allowed with either CsA or CsA-ME. Twelve-hour pharmacokinetic profiling was performed at the end of periods 1 and 2.
Both the mean area under the concentration-versus-time curve and the mean maximum blood concentration of cyclosporine-both normalized for dose-were significantly increased: by 66% and 109%, respectively, in patients receiving CsA-ME compared with those receiving CsA in group 1 and by 39% and 75%, respectively, in group 2. During this study, liver function remained stable, and serum creatinine and blood pressure did not differ significantly between treatment groups.
This study shows increased bioavailability in all patients converted to CsA-ME, with the greatest increase seen in patients with the lowest initial cyclosporine bioavailability. The tolerability was similar between the two formulations during this study.
在一项开放标签、多中心、随机交叉试验中，对两种年龄组（1组，1 - 5岁；2组，6 - 17岁）的小儿肝移植维持治疗患者，比较了原研环孢素制剂（CsA）和新制剂微乳型环孢素（CsA - ME）的口服生物利用度。所有患者移植后至少已过去6个月，且正在接受CsA维持治疗。
在研究期1（第1天至第14天），患者按与维持治疗相同的每日两次剂量服用CsA或CsA - ME。进入期2（第15天至第28天）后，患者以1:1毫克的剂量比转换为另一种制剂。在第29天，所有患者恢复到研究开始时给予的CsA治疗，并在第35天进行随访。CsA或CsA - ME均不允许进行剂量调整。在期1和期2结束时进行12小时的药代动力学分析。
环孢素的浓度 - 时间曲线下平均面积和平均最大血药浓度（均按剂量进行了标准化）均显著升高：与1组中接受CsA的患者相比，接受CsA - ME的患者分别升高了66%和109%，2组中分别升高了39%和75%。在本研究期间，肝功能保持稳定，各治疗组之间血清肌酐和血压无显著差异。
本研究表明，所有转换为CsA - ME的患者生物利用度均有所提高，初始环孢素生物利用度最低的患者升高幅度最大。在本研究中，两种制剂的耐受性相似。
