Model-independent method of analyzing input in linear pharmacokinetic systems having polyexponential impulse response II: Numerical evaluation.

The investigated method is based on an exact mathematical solution to the deconvolution problem of linear pharmacokinetic systems with a polyexponential impulse response. The accuracy of the method is determined only by how well the curves fitted to the intravenous and absorption data represent the true drug level. Consequently, the method enables objective evaluation of the input. It permits the user to assess whether discrepancies in a calculated input are due to an improper data representation, as judged from the fitted curves, to the inherent nature of the data, or to a violation of the pharmacokinetic assumptions. The method is compared to another method using simulated data containing various degrees of random noise. The accuracy of the two methods was not significantly different and was of the same magnitude as the noise level of the data. The theoretical properties of the two methods and their expected performance in various pharmacokinetic situations are discussed. The method is applied to pentobarbital data from oral and intravenous administrations.