Using Front-end Kinetics to Optimize Target-controlled Drug Infusions

Abstract

Because three-compartment models based on drug concentration histories obtained after rapid intravenous administration do not characterize VC accurately, TCIs based on them produce concentrations exceeding the target. A model capable of producing TCIs deviating minimally from the target can be derived from data obtained during and after a brief drug infusion.

Estudio comparativo entre inducción rápida y lenta de propofol en infusión objetivo-controlada: concentración de propofol prevista en la región de acción. Ensayo clínico aleatorizado

“…Ese retraso depende, entre otros factores, de la extracción pulmonar del propofol en el primer paso 14,15 . En el modelo farmacocinético de Marsh ese error inicial es evidente durante los 5 primeros minutos, lo que convierte a ese modelo en algo poco preciso en esos minutos iniciales 7 .…”

“…Como la dosis de bolo depende del tamaño del compartimento central, supervalorar ese volumen puede traer como resultado un gran bolo, que podrá exceder la Ca toda vez que el objeto se aumente 14,15 .…”

Clinical Pharmacokinetic Applications of Recirculatory Models

“…The use of a reasonable estimate of Vc as the sum of Vc and V ND (non-distributive distribution volume) from the recirculatory model was recommended. Accordingly, it was proposed that better estimates of Vc can be obtained from studies in which the drug of interest is administered in a short-term intravenous infusion in order to avoid many of the mistaken assumptions made when fitting data obtained after rapid intravenous drug administration [42].…”

Presenting Data versus Predictions as Basic Scientific Information: Target-controlled Infusions versus Microgram per Kilogram per Minutes

“…6 Errors in the predicted plasma drug concentrations can lead to substantial errors in the pharmacodynamic model and erroneous conclusions. 7,8 Therefore, it is highly desirable that pharmacokinetic-pharmacodynamic studies measure a sufficient number of plasma drug concentrations at times that will allow optimal characterization of pharmacokinetics, including early drug distribution, 9 and subsequent accurate and precise estimation of the pharmacodynamic parameters. 10 Such models could improve the accuracy of effect-site targeted target-controlled infusion 8 more than is possible by reworking flawed existing models.…”