PHARMACOKINETIC MODELING

For radiation dosimetry calculations of radiolabeled monoclonal antibo dies, (MAb), pharmacokinetics are critical. Specifically, pharmacokine tic modeling is a useful component of estimation of cumulated activity in various source organs in the body. It is thus important to formula te general methods of pharmacokinetic modeling and of pharmacokinetic data reduction, leading to cumulated activities. In this paper differe nt types of models are characterized as ''empirical,'' ''analytical,'' and ''compartmental'' pharmacokinetic models. There remains a pressin g need for quantitative studies in man for a proper understanding of t he pharmacokinetics of MAb. Pharmacokinetic modeling of radiolabeled M Ab in vivo has relied on relatively limited studies in man and complem entary detailed measurements in animals. In either case, any model cho sen for analysis of such data is inevitably based on measurements of l imited accuracy and precision as well as assumptions regarding human p hysiology. Very few macroscopic compartmental pharmacokinetic models f or MAb, have been tested over a range of conditions to determine their predictive ability. Extracorporeal immunoadsorption represents one ap proach for drastically altering the biokinetics of antibody distributi on, and may serve to validate a given pharmacokinetic model. In additi on to macroscopic modeling, the microscopic evaluation of the time-dep endent distribution of radiolabeled MAb in tissues is of utmost import ance for a proper understanding of the kinetics and radiobiologic effe ct. Many tumors do not exhibit homogeneous uptake. A mathematical unde rstanding of that distribution is thus essential for accurate tumor do simetry estimates. This review summarizes methodologies for pharmacoki netic modeling, critically reviews specific pharmacokinetic models and demonstrates the capability of modeling for predictive calculations o f altered pharmacokinetics, emphasizing its use in dosimetric calculat ions.