Bolus pharmacokinetics: moving beyond mass-based dosing to guide drug administration
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ORIGINAL PAPER
Bolus pharmacokinetics: moving beyond mass-based dosing to guide drug administration Elie Sarraf1 Received: 3 April 2020 / Accepted: 10 August 2020 Ó Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Despite the common approach of bolus drug dosing using a patient’s mass, a more tailored approach would be to use empirically derived pharmacokinetic models. Previously, this could only be possible though the use of computer simulation using programs which are rarely available in clinical practice. Through mathematical manipulations and approximations, a simplified set of equations is demonstrated that can identify a bolus dose required to achieve a specified target effect site concentration. The proposed solution is compared against simulations of a wide variety of pharmacokinetic models. This set of equations provides a near-identical solution to the simulation approach. A boundary condition is established to ensure the derived equations have an acceptable error. This approach may allow for more precise administration of medications with the use of point of care technology and potentially allows for pharmacokinetic dosing in artificial intelligence problems. Keywords Bolus dosing Computational pharmacokinetics Peak drug effect Target controlled infusion
Introduction In anesthesiology and in many other branches of medicine, the general rule of thumb is that when administrating a medication through an intravenous bolus, the dose required is given as a function of the patient’s mass [1, 2]. For example, the standard induction dose of propofol is 2–2.5 mg/kg ‘‘with dose varying according to age and surgery’’ [3]. The practice of mass-based dosing persists despite the development of mathematical models that have identified many patient factors that influence drug pharmacokinetics. To account for the variability that may result from height and sex, especially in the context of obesity, different measurements of body composition have been suggested to guide dosing such as lean body mass (LBM)
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10928-020-09709-w) contains supplementary material, which is available to authorized users. & Elie Sarraf [email protected] 1
Department of Anesthesiology & Perioperative Medicine, Penn State Health Milton S. Hershey Medical Center, 500 University Drive, H187, Hershey, PA 17033, USA
[1, 2, 4], though not without controversy [5, 6]. Continuing to rely on mass-based drug dosing, while simplifying clinical care, leaves a lot of room for error, especially when compared to empirically-derived pharmacokinetic models. Age and other parameters, such as height, gender, and other features, can have a rather significant effect [7]. These points are demonstrated in the Online Appendix A: ‘‘Does bolus dosing by mass alone make sense?’’, where it is explained how the range of propofol for the induction of a 100 kg patient can be between 150 and 300 mg from the pharmacokinetic profile alone. It is also d
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