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https://hdl.handle.net/2440/6015
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Type: | Journal article |
Title: | Calculating the hybrid (macro) rate constants of a three-compartment mamillary pharmacokinetic model from known micro-rate constants |
Author: | Upton, R. |
Citation: | Journal of Pharmacological and Toxicological Methods, 2004; 49(1):65-68 |
Publisher: | Elsevier Science Inc |
Issue Date: | 2004 |
ISSN: | 1056-8719 1873-488X |
Abstract: | <h4>Introduction</h4>While there are published equations for calculating the hybrid (macro) rates constants (lambda1 and lambda2) of a two-compartment mamillary pharmacokinetic model from its micro-rate constants (e.g., k12, k21 etc.), there appears to be no report of an analogous method for a three-compartment model. The hybrid rate constants are the exponents of the multi-exponential equation describing the time-course of the predicted blood concentrations.<h4>Methods</h4>Using the method of Wagner, the differential equations of a three-compartment model were solved by transformation into the Laplace domain then matrix manipulation. The inversion of the result back into the time domain requires finding the roots of a cubic polynomial. The equations of a convenient method for doing so are reported. This "analytical" method for finding the hybrid rate constants was compared with an alternative "simulation and fitting" method. For this, a model with known micro-rate constants was used to predict a time-course of blood concentrations for a bolus dose, which was then fitted to a tri-exponential equation to find the hybrid rate constants.<h4>Results</h4>The hybrid rate constants for the two methods were identical to at least four significant figures, confirming the validity of the analytical equations.<h4>Discussion</h4>The equations presented here fill a gap in the pharmacokinetic literature, which may be useful in some applications considering the widespread use of the three-compartment mamillary pharmacokinetic model. |
Keywords: | Propofol Pharmacokinetics Algorithms Models, Biological Time Factors |
DOI: | 10.1016/j.vascn.2003.09.001 |
Published version: | http://dx.doi.org/10.1016/j.vascn.2003.09.001 |
Appears in Collections: | Anaesthesia and Intensive Care publications Aurora harvest |
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