PHARMACOKINETIC-BASED MINIBOLUS DELIVERY AS AN ALTERNATIVE TO CONTINUOUS-INFUSION FOR DRUGS THAT EXHIBIT A BIOPHASE LAG

The presence of a biophase compartment in a pharmacokinetic model indi cates that the response to an administered dose of drug is damped such that the time to peak effect occurs after the peak concentration in t he bloodstream. This phenomenon, which is common to most intravenous a nesthetic agents, can be exploited by a drug delivery method that admi nisters minibolus doses of drug rather than a continuous infusion. Thr ough analysis of the frequency response behavior of the biophase compa rtment, a bolus magnitude and dose frequency or interval (1/frequency) can be chosen such that the oscillation in dug effect is minimized ev en though the plasma concentration may be changing significantly with each supplemental dose. A pharmacokinetic and pharmacodynamic based me thod for calculating the bolus dose si-e and dosing interval is presen ted The trade-off between close interval and change in drug effect is exemplified through computer simulation of this strategy applied to de livery of the neuromuscular blocking agent pancuronium. The method pro vides a repetitive perturbation to the pharmacokinetic and pharmacodyn amic system that can aid in model parameter identification during clos ed loop applications.