Abstract
Pharmacokinetic (PK) studies assume that the tracer's PK is equivalent to the parent compound. This assumption is often violated. The aim of this work is to present a method enabling the ideal tracer PK, i.e. the PK of the parent compound, to be predicted from the non-ideal tracer. The procedure uses a disposition decomposition-recomposition (DDR) that assumes that the labeling mainly changes the elimination kinetics while the distribution kinetics is not significantly affected. In the DDR procedure an elimination rate constant correction factor (kCOR) is determined from a simultaneously fitting to plasma concentration data resulting from an i.v. injection of both the tracer and the parent compound. The correction factor is subsequently used to predict the ideal tracer PK behavior from the disposition function (i.v. bolus response) of the non ideal tracer. The DDR method when applied to plasma level data of erythropoietin (r-HuEPO) and its iodinated tracer (125I-r-HuEPO) from a high (4000U/kg) and a low (400U/kg) dosing of r-HuEPO in newborn lambs (n=13) resulted in excellent agreements in the elimination rate corrected dispositions in all cases (r=0.995, SD=0.0095). The correction factor did not show a dose dependence (p > 0.05). The correction factors were all larger than 1 (kCOR=1.94, SD=0.519) consistent with a reduction in the EPO elimination by the iodination labeling. The DDR tracer correction methodology produces a better differentiation of the PK of endogenously produced compounds by correcting for the non-ideal PK behavior of chemically produced tracers.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.