An approximate model-independent method to maintain constant plasma levels of intravenous drugs

Abstract

To rapidly achieve and maintain constant plasma concentrations most intravenous drugs must be administered as an initial bolus followed by a combination of exponentially declining plus constant-rate infusions. In the clinical practice of anesthesia and critical care medicine this is often not practical without specialized equipment. In this paper a simpler approach of maintaining approximately constant plasma concentrations is developed using a loading dose with a two-stage infusion scheme (an initial rapid infusion reduced at a given time to a lower rate). Equations are developed for determining the rate of the infusions as well as the duration of the initial infusion by equating moments of the Laplace transform of the approximate infusion to the moments of the Laplace transform of an exact solution. This approach is independent of models and uses as parameters the moments of the curve relating the concentration following a single iv dose of unit magnitude as a function of time. The accuracy of this technique was assessed by computer simulation.