Rouster-Stevens Kelly A, Gursahaney Aneel, Ngai Ka-Leung, Daru Jennifer A, Pachman Lauren M
Wake Forest University Baptist Medical Center, Pediatric Rheumatology, Winston-Salem, North Carolina 27157, USA.
Arthritis Rheum. 2008 Feb 15;59(2):222-6. doi: 10.1002/art.23341.
To determine areas under the curve (AUCs) of oral prednisolone (OP) and intravenous methylprednisolone (IVMP) in patients with juvenile dermatomyositis (DM) and assess the association with nailfold end-row loops (ERLs). Patients with active disease have fewer ERLs that possibly occur in the gastrointestinal tract, impairing absorption of oral medications.
Six patients with juvenile DM received 50 mg/m(2) of OP (day 1) and IVMP (day 2). Blood was drawn at baseline and at 5, 15, 30, 45, 60, and 90 minutes, and hourly (hours 2-8) after each dose. Samples were analyzed by reverse-phase high-performance liquid chromatography for levels of prednisolone and methylprednisolone. AUCs of OP and IVMP were determined by the trapezoid method; pharmacokinetic parameters were obtained using noncompartmental and compartmental analysis. ERLs were determined from freeze-frame video microscopy and nailfold capillaroscopy.
There was a trend toward significance in difference in mean AUC of IVMP (116.72 microg x ml/hour) compared with OP (65.16 microg x ml/hour; P = 0.059). Mean peak concentration was higher for IVMP (34.49 microg/ml) than OP (7.08 microg/ml); mean half-life was shorter for IVMP (1.90 hours) than OP (2.36 hours). There was an inverse association between DeltaAUCs (IVMP AUC - OP AUC) and ERLs (R = -0.68, P = 0.044).
Patients with juvenile DM and ERL loss may have decreased bioavailability of OP compared with IVMP. This can provide the rationale for greater efficacy of IVMP in patients with active vasculopathy of juvenile DM. Further studies investigating the pharmacokinetics and pharmacodynamics of high-dose IVMP need to be performed in patients with juvenile DM.
测定青少年皮肌炎(DM)患者口服泼尼松龙(OP)和静脉注射甲泼尼龙(IVMP)的曲线下面积(AUC),并评估其与甲襞终末排环(ERL)的相关性。活动性疾病患者的ERL较少,可能发生在胃肠道,影响口服药物的吸收。
6例青少年DM患者接受50mg/m²的OP(第1天)和IVMP(第2天)治疗。在基线以及每次给药后5、15、30、45、60和90分钟,以及2至8小时每小时采集血样。通过反相高效液相色谱法分析样本中泼尼松龙和甲泼尼龙的水平。采用梯形法测定OP和IVMP的AUC;使用非房室和房室分析获得药代动力学参数。通过定格视频显微镜检查和甲襞毛细血管镜检查确定ERL。
与OP(65.16μg·ml/小时)相比,IVMP的平均AUC(116.72μg·ml/小时)差异有显著趋势(P = 0.059)。IVMP的平均峰值浓度(34.49μg/ml)高于OP(7.08μg/ml);IVMP的平均半衰期(1.90小时)短于OP(2.36小时)。ΔAUC(IVMP AUC - OP AUC)与ERL之间存在负相关(R = -0.68,P = 0.044)。
与IVMP相比,患有青少年DM和ERL缺失的患者可能OP的生物利用度降低。这可以为IVMP在青少年DM活动性血管病变患者中具有更高疗效提供理论依据。需要对青少年DM患者进行进一步研究,以调查高剂量IVMP的药代动力学和药效学。