COMPARISON OF METHODS TO CALCULATE CYCLOSPORINE-A BIOAVAILABILITY FROM CONSECUTIVE ORAL AND INTRAVENOUS DOSES
COMPARISON OF METHODS TO CALCULATE CYCLOSPORINE-A BIOAVAILABILITY FROM CONSECUTIVE ORAL AND INTRAVENOUS DOSES
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DOI：
10.1007/bf01062270
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发表时间：
1990-08-01
期刊：
影响因子：
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通讯作者：
LINDBERGFREIJS, A
中科院分区：
文献类型：
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作者：
KARLSSON, MO;LINDBERGFREIJS, A
本文研究了21例尿毒症患者口服环孢素A的药代动力学。同时通过非线性回归分析口服给药和随后短期输注后的血药浓度。双指数和三指数处置模型与零级或一级吸收拟合的数据。通常发现具有零级吸收的三指数分布模型最能描述浓度-时间曲线。生物利用度和清除率估计为0.24 ±。0.10和21 .+-. 8 L/hr。这些值与其他模型预测的值仅略有不同。还从假定消除可饱和的三室模型、去卷积程序和基于血药浓度的分析中获得了相似的生物利用度估计值。显著更高的生物利用度（0.34 ± 0.05）。0.13）时，获得的模型独立的AUC校正程序，通常用于计算CyA的生物利用度，被使用。这种差异不能用模型依赖性分析中数据描述不佳来解释，而是用模型独立性分析中的高估来解释，主要是由于所用外推法的错误。因此，通过同时拟合程序，这是一种新的方法来估计CyA的生物利用度，可以避免AUC校正程序的缺点。此外，未来的研究CyA的生物利用度可以设计一个显着更短，更方便的时间长度，如果通过所提出的方法进行分析。
The pharmacokinetics of cyclosporine A (CyA) was studied in 21 uremic patients. The plasma concentrations after an oral dose and a subsequent short-term infusion were analyzed simultaneously by nonlinear regression. Bi- and triexponential disposition models with either zero- or first order absorption were fitted to the data. A triexponential disposition model with zero-order absorption was generally found to best describe the concentration-time profile. The bioavailability and clearance were estimated to be 0.24 .+-. 0.10 and 21 .+-. 8 L/hr, respectively. These values differed only marginally from those predicted by the other models. Similar bioavailability estimates were also obtained from a three-compartment model where elimination was assumed saturable, from a deconvolution procedure, and from analyses based on blood concentrations. Markedly higher bioavailabilities (0.34 .+-. 0.13) were obtained when a model-independent AUC correction procedure, commonly used to calculate CyA bioavailability, was used. The difference could not be explained by poor description of data in the model-dependent analyses, but rather by overestimation in the model-independent analyses mainly due to errors in the extrapolations used. Thus, by the simultaneous fitting procedure, which is a new approach for estimating CyA bioavailability, drawbacks of the AUC correction procedure could be avoided. Further, future studies of CyA bioavailability could be designed with a markedly shorter and more convenient length of time if analyzed by the proposed method.