Spline functions in convolutional modeling of verapamil bioavailability and bioequivalence. I: conceptual and numerical issues

  • J. Popović


A cubic spline function for describing the verapamil concentration profile, resulting from the verapamil absorption input to be evaluated, has been used. With this method, the knots are taken to be the data points, which has the advantage of being computationally less complex. Because of its inherently low algorhythmic errors, the spline method is less distorted and more suitable for further data analysis than others. The method has been evaluated using simulated verapamil delayed release tablet concentration data containing various degrees of random noise. The accuracy of the method was determined by how well the estimates of input rate and extent represented the true values. It was found that the accuracy of the method was of the same order of magnitude as the noise level of the data. Spline functions in convolutional modeling of verapamil formulation bioavailability and bioequivalence, as shown in the numerical simulation investigation, are very powerful additional tools for assessing the quality of new verapamil formulations in order to ensure that they are of the same quality as already registered formulations of the drug. The development of such models provides the possibility to avoid additional or larger bioequivalence and/or clinical trials and to thus help shorten the investigation time and registration period.


Spline convolution input rate simulation verapamil 


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© Springer-Verlag 2006

Authors and Affiliations

  • J. Popović
    • 1
  1. 1.Faculty of MedicinePharmacology DepartmentNovi SadRepublic of Serbia

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