Ketamine Pharmacokinetics
Anesthesiology, vol. 133, pp. 1192–1213
Abstract
BACKGROUND: Several models describing the pharmacokinetics of ketamine are published with differences in model structure and complexity. A systematic review of the literature was performed, as well as a meta-analysis of pharmacokinetic data and construction of a pharmacokinetic model from raw data sets to qualitatively and quantitatively evaluate existing ketamine pharmacokinetic models and construct a general ketamine pharmacokinetic model. METHODS: Extracted pharmacokinetic parameters from the literature (volume of distribution and clearance) were standardized to allow comparison among studies. A meta-analysis was performed on studies that performed a mixed-effect analysis to calculate weighted mean parameter values and a meta-regression analysis to determine the influence of covariates on parameter values. A pharmacokinetic population model derived from a subset of raw data sets was constructed and compared with the meta-analytical analysis. RESULTS: The meta-analysis was performed on 18 studies (11 conducted in healthy adults, 3 in adult patients, and 5 in pediatric patients). Weighted mean volume of distribution was 252 l/70 kg (95% CI, 200 to 304 l/70 kg). Weighted mean clearance was 79 l/h (at 70 kg; 95% CI, 69 to 90 l/h at 70 kg). No effect of covariates was observed; simulations showed that models based on venous sampling showed substantially higher context-sensitive half-times than those based on arterial sampling. The pharmacokinetic model created from 14 raw data sets consisted of one central arterial compartment with two peripheral compartments linked to two venous delay compartments. Simulations showed that the output of the raw data pharmacokinetic analysis and the meta-analysis were comparable. CONCLUSIONS: A meta-analytical analysis of ketamine pharmacokinetics was successfully completed despite large heterogeneity in study characteristics. Differences in output of the meta-analytical approach and a combined analysis of 14 raw data sets were small, indicative that the meta-analytical approach gives a clinically applicable approximation of ketamine population parameter estimates and may be used when no raw data sets are available.
Authors 6
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Leiden University Medical Center · University of Colorado Anschutz
Affiliation as printed
Department of Anesthesiology , Leiden University Medical Center , Leiden , The Netherlands
Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, Colorado, USA (T.K.H.)
From the Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands (J.K., E.O., M.v.V., M.N., A.D.)
Submitted for publication August 9, 2019. Accepted for publication September 4, 2020. Published online first on September 30, 2020
The Ketamine Pharmacokinetic Study Group participants and affiliations are listed in the appendix
This article is accompanied by an editorial on p. 1167
This article is featured in "This Month in Anesthesiology," page 1A
the Department of Anesthesiology, University of Colorado School of Medicine, Aurora, Colorado, USA (T.K.H.)
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Leiden University Medical Center · University of Colorado Anschutz
Affiliation as printed
Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, Colorado, USA (T.K.H.)
From the Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands (J.K., E.O., M.v.V., M.N., A.D.)
Submitted for publication August 9, 2019. Accepted for publication September 4, 2020. Published online first on September 30, 2020
The Ketamine Pharmacokinetic Study Group participants and affiliations are listed in the appendix
This article is accompanied by an editorial on p. 1167
This article is featured in "This Month in Anesthesiology," page 1A
the Department of Anesthesiology, University of Colorado School of Medicine, Aurora, Colorado, USA (T.K.H.)
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Leiden University Medical Center · University of Colorado Anschutz
Affiliation as printed
Department of Anesthesiology , Leiden University Medical Center , Leiden , The Netherlands
Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, Colorado, USA (T.K.H.)
From the Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands (J.K., E.O., M.v.V., M.N., A.D.)
Submitted for publication August 9, 2019. Accepted for publication September 4, 2020. Published online first on September 30, 2020
The Ketamine Pharmacokinetic Study Group participants and affiliations are listed in the appendix
This article is accompanied by an editorial on p. 1167
This article is featured in "This Month in Anesthesiology," page 1A
the Department of Anesthesiology, University of Colorado School of Medicine, Aurora, Colorado, USA (T.K.H.)
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Wright State University · Leiden University Medical Center · Dayton Children's Hospital · University of Colorado Anschutz
Affiliation as printed
Department of Anesthesiology , Leiden University Medical Center , Leiden , The Netherlands ,
Wright State University Boonshoft , School of Medicine , Dayton Children's Hospital , Dayton , Ohio ,
Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, Colorado, USA (T.K.H.)
From the Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands (J.K., E.O., M.v.V., M.N., A.D.)
Submitted for publication August 9, 2019. Accepted for publication September 4, 2020. Published online first on September 30, 2020
The Ketamine Pharmacokinetic Study Group participants and affiliations are listed in the appendix
This article is accompanied by an editorial on p. 1167
This article is featured in "This Month in Anesthesiology," page 1A
the Department of Anesthesiology, University of Colorado School of Medicine, Aurora, Colorado, USA (T.K.H.)
-
Leiden University Medical Center · University of Colorado Anschutz
Affiliation as printed
Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, Colorado, USA (T.K.H.)
From the Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands (J.K., E.O., M.v.V., M.N., A.D.)
Submitted for publication August 9, 2019. Accepted for publication September 4, 2020. Published online first on September 30, 2020
The Ketamine Pharmacokinetic Study Group participants and affiliations are listed in the appendix
This article is accompanied by an editorial on p. 1167
This article is featured in "This Month in Anesthesiology," page 1A
the Department of Anesthesiology, University of Colorado School of Medicine, Aurora, Colorado, USA (T.K.H.)
-
Leiden University Medical Center · University of Colorado Anschutz
Affiliation as printed
Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, Colorado, USA (T.K.H.)
From the Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands (J.K., E.O., M.v.V., M.N., A.D.)
Submitted for publication August 9, 2019. Accepted for publication September 4, 2020. Published online first on September 30, 2020
The Ketamine Pharmacokinetic Study Group participants and affiliations are listed in the appendix
This article is accompanied by an editorial on p. 1167
This article is featured in "This Month in Anesthesiology," page 1A
the Department of Anesthesiology, University of Colorado School of Medicine, Aurora, Colorado, USA (T.K.H.)
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