The in vivo pharmacokinetics of protoporphyrin IX (PpIX) after administration of 5-aminolevulinic acid (ALA) cannot be described accurately by mathematical models using first-order rate processes. We have replaced first-order reaction rates by dose-dependent (Michaelis–Menten [MM]) reaction rates in a mathematical compartment model. Different combinations of first-order and dose-dependent reaction rates were evaluated to see which one would improve the goodness-of-fit to experimentally determined in vivo PpIX fluorescence kinetics as a function of concentration. The mathematical models that were evaluated are all based on a three-compartment model for drug distribution, conversion to PpIX and subsequent conversion to heme. Implementation of dose-dependent reaction rates improved the goodness-of-fit and enabled interpolation to other drug doses. For most data sets the time constant for delivery to the target cells turned out to be dose dependent. For all data sets the use of MM rates for the conversion of ALA to PpIX yielded better fits. The clearance of PpIX turned out to be a first-order process for all doses and types of administration. Fluorescence curves measured on a specific tissue type but obtained in different studies with different measurement techniques could be described with a single set of parameters.
You have requested a machine translation of selected content from our databases. This functionality is provided solely for your convenience and is in no way intended to replace human translation. Neither BioOne nor the owners and publishers of the content make, and they explicitly disclaim, any express or implied representations or warranties of any kind, including, without limitation, representations and warranties as to the functionality of the translation feature or the accuracy or completeness of the translations.
Translations are not retained in our system. Your use of this feature and the translations is subject to all use restrictions contained in the Terms and Conditions of Use of the BioOne website.
Vol. 74 • No. 2