Weiss M
Department of Pharmacology, Martin Luther University Halle-Wittenberg, Germany.
Pharm Res. 1996 Oct;13(10):1547-53. doi: 10.1023/a:1016039931663.
Flexible parametric models describing the input process after extravascular drug administration are needed for the assessment of absorption rate and the use of population methods in bioavailability and bioequivalence studies.
The oral concentration-time curve modeled as the product of the input and disposition function in the Laplace domain was obtained by numerical inversion methods for parameter estimation. The utility of the inverse Gaussian input density was examined using bioavailability data of an extended-release dosage form. Measures of rate of absorption and the cumulative absorbed amount profile were defined in terms of the estimated model parameters.
Accurate estimation of absorption parameters was achieved by simultaneous fitting of the extravascular and intravascular data (describing the latter by a triexponential function). The new input function allowed a direct estimation of both extent of absorption and mean absorption time.
The findings suggest that the inverse Gaussian density is a useful input function. Its flexibility may reduce the effect of model misspecification in parameter estimation. All parameters can be readily interpreted in terms of the absorption process.
在生物利用度和生物等效性研究中，评估吸收速率以及使用群体方法时，需要灵活的参数模型来描述血管外给药后的输入过程。
通过数值反演方法获得拉普拉斯域中作为输入和处置函数乘积建模的口服浓度-时间曲线，用于参数估计。使用缓释剂型的生物利用度数据检验了逆高斯输入密度的实用性。根据估计的模型参数定义了吸收速率和累积吸收量曲线的度量。
通过同时拟合血管外和血管内数据（用三指数函数描述后者）实现了吸收参数的准确估计。新的输入函数允许直接估计吸收程度和平均吸收时间。
研究结果表明逆高斯密度是一种有用的输入函数。其灵活性可能会降低参数估计中模型错误指定的影响。所有参数都可以根据吸收过程轻松解释。
