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Two-Compartment Modeling and Computer Programs to Find the Optimal Intravenous Drug Dosage Regimens

Kwang S. Kim and Laurent Simon. Otto H. York Department of Chemical Engineering, New Jersey Institute of Technology, University Heights, Newark, NJ 07102

A user-friendly computer program was developed to determine optimal drug-dosage regimens using a two-compartment pharmacokinetic model. The results are applicable for intravenous bolus injections (i.v. bolus) followed by a continuous infusion (i.v. infusion). To decrease the time it takes to reach a desired therapeutic plasma concentration while satisfying constraints (i.e., therapeutic window), the algorithm estimates the sizes of a set number of bolus doses given at specific times and the infusion rate. Published pharmacokinetic parameters, i.e., intercompartment transfer rate coefficients and apparent Michaelis-Menten constants of theophylline, were used to illustrate the methodology. Drug concentration profiles in the central (plasma) and peripheral cell compartments were solved by orthogonal collocation method in the Mathematica (Wolfram Research, Inc.) environment. This technique has the potential to assist in providing customized patient care by helping to identify individualized drug doses that are both efficacious and safe.