Advanced search
1 file | 1.12 MB Add to list

Clinical pharmacokinetics and pharmacodynamics of propofol

(2018) CLINICAL PHARMACOKINETICS. 57(12). p.1539-1558
Author
Organization
Abstract
Propofol is an intravenous hypnotic drug that is used for induction and maintenance of sedation and general anaesthesia. It exerts its effects through potentiation of the inhibitory neurotransmitter -aminobutyric acid (GABA) at the GABA(A) receptor, and has gained widespread use due to its favourable drug effect profile. The main adverse effects are disturbances in cardiopulmonary physiology. Due to its narrow therapeutic margin, propofol should only be administered by practitioners trained and experienced in providing general anaesthesia. Many pharmacokinetic (PK) and pharmacodynamic (PD) models for propofol exist. Some are used to inform drug dosing guidelines, and some are also implemented in so-called target-controlled infusion devices, to calculate the infusion rates required for user-defined target plasma or effect-site concentrations. Most of the models were designed for use in a specific and well-defined patient category. However, models applicable in a more general population have recently been developed and published. The most recent example is the general purpose propofol model developed by Eleveld and colleagues. Retrospective predictive performance evaluations show that this model performs as well as, or even better than, PK models developed for specific populations, such as adults, children or the obese; however, prospective evaluation of the model is still required. Propofol undergoes extensive PK and PD interactions with both other hypnotic drugs and opioids. PD interactions are the most clinically significant, and, with other hypnotics, tend to be additive, whereas interactions with opioids tend to be highly synergistic. Response surface modelling provides a tool to gain understanding and explore these complex interactions. Visual displays illustrating the effect of these interactions in real time can aid clinicians in optimal drug dosing while minimizing adverse effects. In this review, we provide an overview of the PK and PD of propofol in order to refresh readers' knowledge of its clinical applications, while discussing the main avenues of research where significant recent advances have been made.
Keywords
TARGET-CONTROLLED INFUSION, HEPATIC BLOOD-FLOW, CORTICAL EFFECTIVE, CONNECTIVITY, SHORT-TERM SEDATION, BISPECTRAL INDEX, CESAREAN-SECTION, NITROUS-OXIDE, POPULATION PHARMACOKINETICS, HEMODYNAMIC-RESPONSES, INTRAVENOUS PROPOFOL

Downloads

  • 8599499.pdf
    • full text
    • |
    • open access
    • |
    • PDF
    • |
    • 1.12 MB

Citation

Please use this url to cite or link to this publication:

MLA
Sahinovic, Marko M, Michel Struys, and Anthony R Absalom. “Clinical Pharmacokinetics and Pharmacodynamics of Propofol.” CLINICAL PHARMACOKINETICS 57.12 (2018): 1539–1558. Print.
APA
Sahinovic, M. M., Struys, M., & Absalom, A. R. (2018). Clinical pharmacokinetics and pharmacodynamics of propofol. CLINICAL PHARMACOKINETICS, 57(12), 1539–1558.
Chicago author-date
Sahinovic, Marko M, Michel Struys, and Anthony R Absalom. 2018. “Clinical Pharmacokinetics and Pharmacodynamics of Propofol.” Clinical Pharmacokinetics 57 (12): 1539–1558.
Chicago author-date (all authors)
Sahinovic, Marko M, Michel Struys, and Anthony R Absalom. 2018. “Clinical Pharmacokinetics and Pharmacodynamics of Propofol.” Clinical Pharmacokinetics 57 (12): 1539–1558.
Vancouver
1.
Sahinovic MM, Struys M, Absalom AR. Clinical pharmacokinetics and pharmacodynamics of propofol. CLINICAL PHARMACOKINETICS. 2018;57(12):1539–58.
IEEE
[1]
M. M. Sahinovic, M. Struys, and A. R. Absalom, “Clinical pharmacokinetics and pharmacodynamics of propofol,” CLINICAL PHARMACOKINETICS, vol. 57, no. 12, pp. 1539–1558, 2018.
@article{8599499,
  abstract     = {Propofol is an intravenous hypnotic drug that is used for induction and maintenance of sedation and general anaesthesia. It exerts its effects through potentiation of the inhibitory neurotransmitter -aminobutyric acid (GABA) at the GABA(A) receptor, and has gained widespread use due to its favourable drug effect profile. The main adverse effects are disturbances in cardiopulmonary physiology. Due to its narrow therapeutic margin, propofol should only be administered by practitioners trained and experienced in providing general anaesthesia. Many pharmacokinetic (PK) and pharmacodynamic (PD) models for propofol exist. Some are used to inform drug dosing guidelines, and some are also implemented in so-called target-controlled infusion devices, to calculate the infusion rates required for user-defined target plasma or effect-site concentrations. Most of the models were designed for use in a specific and well-defined patient category. However, models applicable in a more general population have recently been developed and published. The most recent example is the general purpose propofol model developed by Eleveld and colleagues. Retrospective predictive performance evaluations show that this model performs as well as, or even better than, PK models developed for specific populations, such as adults, children or the obese; however, prospective evaluation of the model is still required. Propofol undergoes extensive PK and PD interactions with both other hypnotic drugs and opioids. PD interactions are the most clinically significant, and, with other hypnotics, tend to be additive, whereas interactions with opioids tend to be highly synergistic. Response surface modelling provides a tool to gain understanding and explore these complex interactions. Visual displays illustrating the effect of these interactions in real time can aid clinicians in optimal drug dosing while minimizing adverse effects. In this review, we provide an overview of the PK and PD of propofol in order to refresh readers' knowledge of its clinical applications, while discussing the main avenues of research where significant recent advances have been made.},
  author       = {Sahinovic, Marko M and Struys, Michel and Absalom, Anthony R},
  issn         = {0312-5963},
  journal      = {CLINICAL PHARMACOKINETICS},
  keywords     = {TARGET-CONTROLLED INFUSION,HEPATIC BLOOD-FLOW,CORTICAL EFFECTIVE,CONNECTIVITY,SHORT-TERM SEDATION,BISPECTRAL INDEX,CESAREAN-SECTION,NITROUS-OXIDE,POPULATION PHARMACOKINETICS,HEMODYNAMIC-RESPONSES,INTRAVENOUS PROPOFOL},
  language     = {eng},
  number       = {12},
  pages        = {1539--1558},
  title        = {Clinical pharmacokinetics and pharmacodynamics of propofol},
  url          = {http://dx.doi.org/10.1007/s40262-018-0672-3},
  volume       = {57},
  year         = {2018},
}

Altmetric
View in Altmetric
Web of Science
Times cited: