Division of Nephrology, Ospedale la Carità, Via Ospedale, 6600 Locarno, Switzerland.
BMC Nephrol. 2011 Feb 18;12:11. doi: 10.1186/1471-2369-12-11.
The increasing use of erythropoietins with long half-lives and the tendency to lengthen the administration interval to monthly injections call for raising awareness on the pharmacokinetics and risks of new erythropoietin stimulating agents (ESA). Their pharmacodynamic complexity and individual variability limit the possibility of attaining comprehensive clinical experience. In order to help physicians acquiring prescription abilities, we have built a prescription computer model to be used both as a simulator and education tool.
The pharmacokinetic computer model was developed using Visual Basic on Excel and tested with 3 different ESA half-lives (24, 48 and 138 hours) and 2 administration intervals (weekly vs. monthly). Two groups of 25 nephrologists were exposed to the six randomised combinations of half-life and administration interval. They were asked to achieve and maintain, as precisely as possible, the haemoglobin target of 11-12 g/dL in a simulated naïve patient. Each simulation was repeated twice, with or without randomly generated bleeding episodes.
The simulation using an ESA with a half-life of 138 hours, administered monthly, compared to the other combinations of half-lives and administration intervals, showed an overshooting tendency (percentages of Hb values > 13 g/dL 15.8 ± 18.3 vs. 6.9 ± 12.2; P < 0.01), which was quickly corrected with experience. The prescription ability appeared to be optimal with a 24 hour half-life and weekly administration (ability score indexing values in the target 1.52 ± 0.70 vs. 1.24 ± 0.37; P < 0.05). The monthly prescription interval, as suggested in the literature, was accompanied by less therapeutic adjustments (4.9 ± 2.2 vs. 8.2 ± 4.9; P < 0.001); a direct correlation between haemoglobin variability and number of therapy modifications was found (P < 0.01).
Computer-based simulations can be a useful tool for improving ESA prescription abilities among nephrologists by raising awareness about the pharmacokinetic characteristics of the various ESAs and recognizing the factors that influence haemoglobin variability.
半衰期较长的红细胞生成素的使用不断增加，并且倾向于将给药间隔延长至每月注射，这就需要提高对新型红细胞生成刺激剂（ESA）的药代动力学和风险的认识。它们的药效学复杂性和个体可变性限制了获得全面临床经验的可能性。为了帮助医生获得处方能力，我们构建了一个处方计算机模型，该模型既可用作模拟器，也可用作教育工具。
使用 Visual Basic 在 Excel 上开发了药代动力学计算机模型，并使用 3 种不同的 ESA 半衰期（24、48 和 138 小时）和 2 种给药间隔（每周 vs. 每月）进行了测试。两组 25 名肾病学家接受了半衰期和给药间隔的六种随机组合。他们被要求尽可能精确地实现并维持 11-12g/dL 的血红蛋白目标，治疗一名模拟的初治患者。每次模拟重复两次，有无随机生成的出血事件。
与半衰期和给药间隔的其他组合相比，使用半衰期为 138 小时、每月给药的 ESA 的模拟显示出过度反应趋势（Hb 值>13g/dL 的百分比为 15.8%±18.3%vs.6.9%±12.2%；P<0.01），随着经验的增加，这种趋势迅速得到纠正。半衰期为 24 小时、每周给药时，处方能力似乎最佳（在目标范围内的能力评分指数值为 1.52±0.70vs.1.24±0.37；P<0.05）。正如文献中所建议的那样，每月的给药间隔期伴随着较少的治疗调整（4.9±2.2 次 vs.8.2±4.9 次；P<0.001）；血红蛋白变异性与治疗调整次数之间存在直接相关性（P<0.01）。
基于计算机的模拟可以通过提高对各种 ESAs 的药代动力学特征的认识，并认识到影响血红蛋白变异性的因素，成为提高肾病学家 ESA 处方能力的有用工具。
