The hybrid model: a new pharmacokinetic model for computer-controlled infusion pumps.
Classical pharmacokinetic models used in computer-controlled infusion pumps (CCIPs) assume instantaneous mixing of drug in blood; however, the average recirculation time of blood in man is approximately one minute. To investigate the effects of recirculation dynamics on the transient performance of CCIPs, we propose a hybrid physiologically-based pharmacokinetic model for the narcotic alfentanil. A three-compartment model was derived from the response of the hybrid model to a short infusion and used to compute a CCIP infusion targeting 450 micrograms/l. For this infusion, the hybrid model predicts that the arterial plasma concentration will overshoot the target concentration by 39 percent with an average prediction error of 3 percent. The overshoot and average prediction error increase to 100 and 25 percent respectively when using a three-compartment pharmacokinetic model derived from a bolus. The overshoot can be reduced by decreasing the maximum possible infusion rate, or by increasing the zero-order hold infusion interval.
Stanford University School of Medicine, Department of Anesthesia, Palo Alto, 94305.
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Wada
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Ward
D015760:Alfentanil / Q000493:pharmacokinetics; D003198:Computer Simulation; D004360:Drug Therapy, Computer-Assisted; D007260:Infusion Pumps; D007262:Infusions, Intravenous; D008954:Models, Biological; D010599:Pharmacokinetics
D015760:Alfentanil