PharmacokineticsandPharmacodynamics.docVIP

The Pharmacokinetic and Pharmacodynamic Basis of Target Controlled Infusion Steven L. Shafer, M.D. Staff Anesthesiologist, Palo Alto VA Health Care System Associate Professor of Anesthesia, Stanford University Address: Anesthesiology Service (112A) PAVAHCS 3801 Miranda Ave Palo Alto, CA 94304 USA Phone 650 852-3419 FAX: 650 852-3414 E-mail: Steven.Shafer@Stanford.Edu Supported in part by the Merit Review Program of the Department of Veterans Affairs. Portions previously published by Steven L. Shafer (used with permission). With the introduction of the Diprifusor( in Europe by Zeneca Pharmaceuticals there is increasing interest in Target Controlled Drug Delivery. Although the Diprifusor is the first commercially produced target controlled infusion device, the concept was introduced in 1968 by Krüger-Theimer. In 1981 Schwilden expanded on these efforts to describe a general method of rapidly reaching and maintaining a constant plasma drug concentration. The first implementation of Computer Assisted Total Intravenous Anesthesia was the CATIA device developed by Schüttler, Schwilden, and Stoekel and reported in 1983. The technology rapidly spread, and in 1985 Ausems, Stanski, and Hug reported on their work with the “TIAC” system in the Netherlands while Avis, Reves, and colleagues reported on their “CACI” system in the United States. In 1998 closed form mathematical solutions for target controlled delivery systems were published by Shafer and Jacobs and implemented in the “STANPUMP” and “CACI II” systems, respectively. By the time the first prototype of the Diprifusor was introduced in 1990 by White and Kenny the technology was mature. It is primarily because of regulatory issues that the commercial introduction has lagged so far behind the scientific developments. Pharmacokinetics and pharmacodynamics provide the scientific foundations of target controlled drug delivery. This review will first present the basic concepts of pharmacokinetics and