Improving drug dosing in hospitalized patients: automated modeling of pharmacokinetics for individualization of drug dosage regimens

Abstract

Many clinically useful drugs have a narrow range of blood concentrations which are both safe and efficacious. Inter-individual and intra-individual variations in drug disposition are important factors causing blood concentrations of drug to fall outside of the therapeutic range. Modeling of the pharmacokinetics of the individual offers an effective approach to the problem of variation in drug disposition. Previous approaches for the modeling of individual pharmacokinetics have required either extensive computations or access to computer software and hardware in the clinical environment, and special expertise to interpret the results. This paper describes a prototype computer program. PK Monitor, which can, when connected with an appropriate interface, automatically monitor drug dosing and recommend changes that may be required to obtain blood concentrations in the therapeutic range. The software can also detect the occurrence of change in drug disposition which will lead to concentrations outside of the therapeutic range, identify potentially erroneous blood concentration measurements, and assess the need for further blood concentration measurements. This program will be an integral part of the MENTOR therapeutic monitoring system of programs. PK Monitor awaits a complete evaluation with the rest of the MENTOR system, but preliminary simulations suggest reasonable sensitivity and specificity in monitoring for unexpected data and change.