Research Articles
Novel Deconvolution Method for Linear Pharmacokinetic Systems with Polyexponential Impulse Response

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Abstract

A novel least-squares deconvolution method for estimating the rate and the extent of drug input into the systemic circulation is presented. The method is based on a polyexponential approximation of the impulse response and a polynomial approximation of the input rate. The method, which is readily implemented on a computer using any multiple linear regression program with a zero-intercept option, is compared to two other deconvolution methods using simulated data with various degrees of random noise added. It appears to have several significant advantages. The method is applied to plasma pentobarbital level data from oral and intravenous administration. The assumptions and limitations of deconvolution methods for analyzing drug input into the blood are discussed.

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    Citation Excerpt :

    Numerical deconvolution is a well-established mathematical tool and has been extensively applied in pharmaceutical research and industry. When this tool is used for in vitro-in vivo correlation, human body is assumed as a linear time-invariant system, which is different from compartmental approach [33–40]. A linear system, from pharmacokinetics point of view, may be described as that: if C1(t) and C2(t) are the plasma concentrations of a drug following an intravenous (IV) dose D1 and D2 respectively, for a linear system an IV dose D1 + D2 will give the plasma concentration C1(t)+ C2(t).

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