Yasuda K, Goshima E, Adachi K, Fuwa Y, Yamakita N, Miura K
Third Department of Internal Medicine, Gifu University School of Medicine, Japan.
J Clin Endocrinol Metab. 1990 Apr;70(4):957-64. doi: 10.1210/jcem-70-4-957.
To determine the pharmacokinetic changes of prednisolone associated with differing therapy regimens, we studied 15 patients with various diseases who were treated with daily doses of prednisolone and were then placed on an intermittent regimen, [administration for 4 consecutive days (on-day period), followed by 3 days cessation (off-day period)]. The mean duration of the study and the mean total dosage were 1.6 months and 2.4 g in the daily period, respectively, and 4.7 months and 3.5 g in the intermittent period, respectively. Blood was drawn for 6 h after iv administration of 20 mg prednisolone (average, 0.36 mg/kg). Plasma total and free prednisolone concentrations were measured by RIA. On-day and off-day tests were performed during the same week. The mean MCR of both total and free prednisolone decreased significantly in the daily and on-day periods compared with the pretreatment values. The decreased MCR during the on-day period was restored to the pretreatment level during the off-day period. A similar trend was observed in the changes in half-life, prolongation in the daily and on-day periods compared with the pretreatment value, and restoration to the pretreatment level during the off-day period. These alterations were not associated with the total duration or the total dosage of prednisolone administered. The results indicate that the pharmacokinetic parameters of prednisolone may periodically change during the intermittent regimen, and that off-day and on-day parameters are similar to those before therapy and during the daily period, respectively.
为了确定与不同治疗方案相关的泼尼松龙药代动力学变化，我们研究了15例患有各种疾病的患者，这些患者接受每日剂量的泼尼松龙治疗，然后改为间歇治疗方案[连续给药4天（服药期），随后停药3天（停药期）]。研究的平均持续时间和平均总剂量在每日治疗期分别为1.6个月和2.4 g，在间歇治疗期分别为4.7个月和3.5 g。静脉注射20 mg泼尼松龙（平均0.36 mg/kg）后6小时采血。采用放射免疫分析法测定血浆总泼尼松龙和游离泼尼松龙浓度。在同一周内进行服药期和停药期测试。与治疗前值相比，每日治疗期和服药期总泼尼松龙和游离泼尼松龙的平均代谢清除率均显著降低。服药期降低的代谢清除率在停药期恢复到治疗前水平。半衰期变化也观察到类似趋势，与治疗前值相比，每日治疗期和服药期半衰期延长，停药期恢复到治疗前水平。这些改变与所给予的泼尼松龙的总持续时间或总剂量无关。结果表明，泼尼松龙的药代动力学参数在间歇治疗方案期间可能会周期性变化，且停药期和服药期的参数分别与治疗前和每日治疗期相似。
