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Bolus pharmacokinetics: moving beyond mass-based dosing to guide drug administration

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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.

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Notes

  1. At the author’s institution there are over 50 different possible anesthetizing locations.

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Acknowledgements

The author thanks Donald M Mathews, M.D. for his guidance during the writing of the manuscript and William G Tharp, M.D., Ph.D., and Alexander F. Friend, M.S., for their constructive criticism of the manuscript.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Anesthesiology & Perioperative Medicine, Penn State Health Milton S. Hershey Medical Center, 500 University Drive, H187, Hershey, PA, 17033, USA

    Elie Sarraf

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  1. Elie Sarraf
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Contributions

ES: this author designed the study, analyzed the data, and prepared the manuscript.

Corresponding author

Correspondence to Elie Sarraf.

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The author declare that he has no conflict of interest.

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Electronic supplementary material

Below is the link to the electronic supplementary material.

10928_2020_9709_MOESM1_ESM.docx

Supplementary file1 (DOCX 2253 kb). Appendix A—Does bolus dosing by mass alone make sense?: This Appendix demonstrates why a patient’s mass is insufficient to calculate a bolus dose of a medication

10928_2020_9709_MOESM2_ESM.docx

Supplementary file2 (DOCX 32 kb). Appendix B—Deriving the critical equations: This Appendix solves the differential equations governing a compartment model following a bolus dose of a medication. It allows the calculation of the volume of distribution at peak effect, and it demonstrates the relationship between the time to peak effect and ke0

10928_2020_9709_MOESM3_ESM.xlsx

Supplementary file3 (XLSX 20 kb). Appendix C—Schnider bolus worksheet: This is an Excel worksheet to calculate the bolus dose of propofol required to achieve a specified Effect Site concentration goal using the Schnider model

10928_2020_9709_MOESM4_ESM.docx

Supplementary file4 (DOCX 231 kb). Appendix D—TCI solution. This Appendix describes how to construct a “human controlled” TCI algorithm using the equations derived in the manuscript and a standard infusion pump. A sample MATLAB code is also attached

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Sarraf, E. Bolus pharmacokinetics: moving beyond mass-based dosing to guide drug administration. J Pharmacokinet Pharmacodyn 47, 573–581 (2020). https://doi.org/10.1007/s10928-020-09709-w

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  • DOI: https://doi.org/10.1007/s10928-020-09709-w

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