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

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.