泼尼松治疗的系统性红斑狼疮年轻患者稳态时泼尼松龙的药代动力学：一项开放标签、单剂量研究。
Pharmacokinetics of prednisolone at steady state in young patients with systemic lupus erythematosus on prednisone therapy: an open-label, single-dose study.
机构信息
Division of Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
出版信息
Clin Ther. 2011 Oct;33(10):1524-36. doi: 10.1016/j.clinthera.2011.09.015. Epub 2011 Oct 7.
BACKGROUND
Current prednisone dosing in the treatment of young patients with childhood-onset systemic lupus erythematosus (cSLE) is largely based on achieving balance between therapeutic efficacy and toxicity, with weight-based dosing a common clinical practice. Despite the widespread use of prednisone, few attempts have been made to improve its clinical dosing regimen, and response to prednisone therapy remains variable.
OBJECTIVE
The purpose of this study was to characterize the pharmacokinetic (PK) properties of prednisolone, the metabolite of the prodrug prednisone, in cSLE patients and explore the relationship between PK properties and cSLE disease activity.
METHODS
Blood samples were taken 1 hour before the morning prednisone dose and at 20, 40, 60, and 90 minutes, and 2, 3, 4, 6, and 9 hours from 8 patients (ages 12-28 years) after an 8-hour fast. The mean weight-adjusted daily prednisone dose, stable for at least 30 days pre-study, was 0.29 mg/kg/d. PK analysis of prednisolone was performed using noncompartmental analysis with WinNonlin. cSLE disease activity was measured using the British Isles Lupus Assessment Group index and Systemic Lupus Erythematosus Disease Activity Index.
RESULTS
Mean total prednisolone AUC(0-9), prednisone CL/F at steady state, and half-life were 1094 (range, 467-2404) ng/h/mL, 11 (range, 6.7-13.7) L/hr, and 2.6 (range, 1.3-3.9) hours. Mean total prednisolone AUC(0-9) normalized to prednisone dose by weight was 4361 (range, 1136-9580) ng/h/mL/mg/kg. Mean total prednisolone C(max) normalized to prednisone dose by weight was 1097 (range, 301-2211) ng/mL/mg/kg at 1.84 (range, 0.48-4) hours (T(max)). Patients on prednisone had interindividual variability in prednisolone AUC(0-9) (61% CV) and dose-adjusted AUC(0-9) (58% CV).
CONCLUSIONS
Interindividual variability in systemic exposure to prednisolone in cSLE patients was observed.
背景
目前，儿童期起病的系统性红斑狼疮（cSLE）患者接受泼尼松治疗时，主要根据治疗效果和毒性之间的平衡来调整剂量，而基于体重的剂量是一种常见的临床实践。尽管泼尼松的应用广泛，但很少有尝试来改善其临床给药方案，且泼尼松治疗的反应仍存在差异。
目的
本研究旨在描述 cSLE 患者中前体药物泼尼松龙的代谢产物（即泼尼松）的药代动力学（PK）特征，并探讨 PK 特征与 cSLE 疾病活动之间的关系。
方法
在 8 例（年龄 12-28 岁）患者禁食 8 小时后，于第 1 天清晨服用泼尼松前 1 小时及之后 20、40、60 和 90 分钟，以及 2、3、4、6 和 9 小时采集血样。在研究前至少 30 天稳定的平均体重调整的日泼尼松剂量为 0.29 mg/kg/d。采用非房室分析方法，使用 WinNonlin 软件分析泼尼松龙的 PK 数据。使用不列颠群岛狼疮评估组指数和系统性红斑狼疮疾病活动指数来测量 cSLE 疾病活动。
结果
平均总泼尼松龙 AUC（0-9）、稳态时的泼尼松 CL/F 和半衰期分别为 1094（范围，467-2404）ng/h/mL、11（范围，6.7-13.7）L/hr 和 2.6（范围，1.3-3.9）小时。以体重标准化的平均总泼尼松龙 AUC（0-9）与泼尼松剂量之比为 4361（范围，1136-9580）ng/h/mL/mg/kg。以体重标准化的平均总泼尼松龙 C（max）与泼尼松剂量之比为 1097（范围，301-2211）ng/mL/mg/kg，于 1.84（范围，0.48-4）小时达到（T（max））。接受泼尼松治疗的患者中，泼尼松龙 AUC（0-9）（61%CV）和剂量调整的 AUC（0-9）（58%CV）存在个体间差异。
结论
在 cSLE 患者中观察到泼尼松龙全身暴露的个体间变异性。
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