Adaptive and sampled-data control of blood levels of antiarrhythmic drugs

Open-loop infusion techniques can be improved by a computer-controlled drug-infusion pump using a pharmacokinetic model for estimation of the blood level. Unfortunately, in individual patients the pharmacokinetic behavior of most drugs varies considerably from population averages. The authors tested the use of occasional blood samples in direct (closed-loop) and indirect (adaptive) feedback schemes for delivery of the antiarrhythmic drugs procainamide and disopyramide using computer simulation. A third scheme tested was a combination of these two (closed-loop adaptive). Pharmacokinetic parameters of 12 patients were used in computer simulations of feedback control. Using an open-loop infusion, the average mean-square error of the plasma level was 22.8% of the target concentration. With feedback control, this error was reduced to 5.1% or better. It is concluded that systems in which feedback of actual plasma levels can occur within three minutes may greatly improve control of drug infusion