Pharmacokinetics of Modified-Release Prednisone Tablets in Healthy Subjects and Patients With Rheumatoid Arthritis
Pharmacokinetics of Modified-Release Prednisone Tablets in Healthy Subjects and Patients With Rheumatoid Arthritis
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DOI：
10.1177/0091270012444315
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发表时间：
2013-03-01
影响因子：
2.9
通讯作者：
Kirwan, John R.
中科院分区：
文献类型：
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作者：
Derendorf, Hartmut;Ruebsamen, Klaus;Kirwan, John R.
在类风湿关节炎（RA）中，促炎细胞因子的夜间释放不能被内源性糖皮质激素充分抵消，并且与晨僵和疼痛症状相关。夜间服用外源性糖皮质激素比早上常规时间的治疗更能显着减少晨僵，尽管醒来后服用药片对于患者来说是不可接受的。改良释放泼尼松片剂的开发允许在睡前给药，以便在夜间按计划输送糖皮质激素。进行了单中心交叉研究，每个研究对象≥24 名健康受试者，比较单次 5 mg 口服剂量的改良释放泼尼松和常规泼尼松的药代动力学，以及食物对生物利用度的影响。除了缓释片剂中糖皮质激素释放的程序性延迟（C-max 97%，AUC（0-无穷大）101%，90%置信区间在生物等效性所需范围内）之外，制剂的药代动力学参数没有显着差异。饱餐或便餐后给药不影响药代动力学特征，但在禁食条件下生物利用度降低。对 9 名 RA 患者的药代动力学评估证实，睡前（约 22:00 小时）与晚餐或晚餐后服用改良释放泼尼松片会导致糖皮质激素在摄入后 4 至 6 小时内程序化释放。
In rheumatoid arthritis (RA), nocturnal release of proinflammatory cytokines is not adequately counteracted by endogenous glucocorticoid and is associated with symptoms of morning stiffness and pain. Taking exogenous glucocorticoid during the night reduces morning stiffness significantly more than treatment at the conventional time in the morning, although waking to take tablets is unacceptable for patients. Modified-release prednisone tablets were developed to allow administration at bedtime for programmed delivery of glucocorticoid during the night. Single-center crossover studies were conducted, each in >= 24 healthy subjects, to compare the pharmacokinetics of a single 5-mg oral dose of modified-release prednisone and conventional prednisone, as well as the effect of food on bioavailability. There was no substantial difference in pharmacokinetic parameters of the formulations apart from the programmed delay in release of glucocorticoid from the modified-release tablets (C-max 97%, AUC(0-infinity) 101%, 90% confidence intervals within the requisite range for bioequivalence). Administration after a full or light meal did not affect pharmacokinetic characteristics, but bioavailability was reduced under fasted conditions. Pharmacokinetic evaluation in 9 patients with RA confirmed that modified-release prednisone tablets taken at bedtime (around 22:00 h) with or after an evening meal result in programmed release of glucocorticoid 4 to 6 hours after intake.