Modelling Hydrocortisone Pharmacokinetics on a Subcutaneous Pulsatile Infusion Replacement Strategy in Patients with Adrenocortical Insufficiency.
Modelling Hydrocortisone Pharmacokinetics on a Subcutaneous Pulsatile Infusion Replacement Strategy in Patients with Adrenocortical Insufficiency.
复制标题
肾上腺皮质功能不全患者皮下脉冲输注替代策略的氢化可的松药代动力学模型。
DOI：
10.3390/pharmaceutics13060769
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发表时间：
2021-05-21
期刊：
影响因子：
5.4
通讯作者：
Russell GM
中科院分区：
文献类型：
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作者：
Violaris IG;Kalafatakis K;Zavala E;Tsoulos IG;Lampros T;Lightman SL;Tsipouras MG;Giannakeas N;Tzallas A;Russell GM
在糖皮质激素 (GC) 治疗方面，最近的研究利用了皮下氢化可的松 (HC) 输注泵，该泵被编程为全天提供多个 HC 脉冲，目的是恢复正常的昼夜节律和超日 GC 节律。推进新型 HC 替代疗法的一个关键挑战是根据血液中测量的皮质醇水平校准输液泵。然而，重复的血液采样对于检查者和受检者来说都是极大的劳动密集型。这些会议也有成本、耗时并且有时不可行。为了解决这个问题，我们开发了一个药代动力学模型，通过有限数量的血浆皮质醇测量值来近似一天中任何时间点的血浆皮质醇水平值。该模型使用 9 名内源性 GC 合成能力受到破坏的受试者的血浆皮质醇曲线进行了验证。当仅提供四次血浆皮质醇测量值时，该模型准确预测血浆皮质醇水平（平均绝对百分比误差为 14%）。尽管我们的模型不能预测当 HC 以皮下以外的方式给药或在内源性产生 GC 的能力完整的个体中时的 GC 动力学，但我们发现该模型成功地用于支持涉及皮下 HC 输送在内源性合成 GC 能力降低的患者中的临床试验（或实践）。
In the context of glucocorticoid (GC) therapeutics, recent studies have utilised a subcutaneous hydrocortisone (HC) infusion pump programmed to deliver multiple HC pulses throughout the day, with the purpose of restoring normal circadian and ultradian GC rhythmicity. A key challenge for the advancement of novel HC replacement therapies is the calibration of infusion pumps against cortisol levels measured in blood. However, repeated blood sampling sessions are enormously labour-intensive for both examiners and examinees. These sessions also have a cost, are time consuming and are occasionally unfeasible. To address this, we developed a pharmacokinetic model approximating the values of plasma cortisol levels at any point of the day from a limited number of plasma cortisol measurements. The model was validated using the plasma cortisol profiles of 9 subjects with disrupted endogenous GC synthetic capacity. The model accurately predicted plasma cortisol levels (mean absolute percentage error of 14%) when only four plasma cortisol measurements were provided. Although our model did not predict GC dynamics when HC was administered in a way other than subcutaneously or in individuals whose endogenous capacity to produce GCs is intact, it was found to successfully be used to support clinical trials (or practice) involving subcutaneous HC delivery in patients with reduced endogenous capacity to synthesize GCs.