Pharmacokinetics and Dynamics of Ketamine Enantiomers Using a Stereoselective Analytical Method

Geißlinger, Gerd; Hering, W.; Kamp, H.-D.; Brune, Kay

doi:10.1097/00000542-199209001-00331

Cited by 30 publications

(51 citation statements)

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“…In vivo studies in humans have shown higher values for the clearance of S-ket than for R-ket either after administration of the individual enantiomers (Persson et al, 2002;White et al, 1985) or after administration of the racemic mixture (Henthorn et al, 1999;Geisslinger et al, 1993;Ihmsen et al, 2001). Our results also clearly show differences in biotransformation of ketamine and/or norketamine enantiomers resulting in consistently higher plasma concentrations of S-nor than of R-nor.…”

Section: Discussion Pharmacokineticssupporting

confidence: 57%

“…The authors proposed two possible reasons: concentration-dependent N-demethylation and concentration-independent metabolic inversion from R-to S-nor or from R-to S-ket and subsequent metabolism to S-nor. We consider the second suggestion to be rather unlikely because no R-enantiomers were detected after administration of S-ket (Geisslinger et al, 1993;Ihmsen et al, 2001). …”

Section: Discussion Pharmacokineticsmentioning

confidence: 92%

“…These studies do not consider individual enantiomers, and only a few studies consider the stereoselectivity of ketamine (White et al, 1985;Delatour et al, 1991;Geisslinger et al, 1993;Henthorn et al, 1999;Ihmsen et al, 2001;Edwards and Mather, 2001). Significant differences in the pharmacokinetic profile, e.g.…”

Section: Introductionmentioning

confidence: 99%

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Antinociceptive effects, metabolism and disposition of ketamine in ponies under target-controlled drug infusion

Knobloch

Portier

Levionnois

et al. 2006

Toxicology and Applied Pharmacology

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Ketamine is widely used as an anesthetic in a variety of drug combinations in human and veterinary medicine. Recently, it gained new interest for use in long-term pain therapy administered in subanesthetic doses in humans and animals. The purpose of this study was to develop a physiologically based pharmacokinetic (PBPk) model for ketamine in ponies and to investigate the effect of lowdose ketamine infusion on the amplitude and the duration of the nociceptive withdrawal reflex (NWR).A target-controlled infusion (TCI) of ketamine with a target plasma level of 1 μg/ml S-ketamine over 120 min under isoflurane anesthesia was performed in Shetland ponies. A quantitative electromyographic assessment of the NWR was done before, during and after the TCI. Plasma levels of R-/S-ketamine and R-/S-norketamine were determined by enantioselective capillary electrophoresis. These data and two additional data sets from bolus studies were used to build a PBPk model for ketamine in ponies.The peak-to-peak amplitude and the duration of the NWR decreased significantly during TCI and returned slowly toward baseline values after the end of TCI. The PBPk model provides reliable prediction of plasma and tissue levels of R-and S-ketamine and R-and S-norketamine. Furthermore, biotransformation of ketamine takes place in the liver and in the lung via first-pass metabolism. Plasma concentrations of S-norketamine were higher compared to R-norketamine during TCI at all time points. Analysis of the data suggested identical biotransformation rates from the parent compounds to the principle metabolites (R-and S-norketamine) but different downstream metabolism to further metabolites. The PBPk model can provide predictions of R-and S-ketamine and norketamine concentrations in other clinical settings (e.g. horses).

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Section: Discussion Pharmacokineticssupporting

confidence: 57%

Section: Discussion Pharmacokineticsmentioning

confidence: 92%

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Antinociceptive effects, metabolism and disposition of ketamine in ponies under target-controlled drug infusion

Knobloch

Portier

Levionnois

et al. 2006

Toxicology and Applied Pharmacology

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“…Ketamine has been used extensively as an anesthetic agent and the plasma concentrations associated with subanesthetic psychosislike perceptual disturbances are in the range of 0.5-1 M, 28 and with anesthesia setting in at concentrations in the 10-100 M range. [29][30][31] Further, brain concentrations are known to be several fold higher than plasma concentrations, 32 suggesting that even the subanesthetic psychosis-like perceptual disturbances occur only at brain concentrations in the one to few micromolar range. Since the affinities of ketamine for the NMDA receptors as well as for the dopamine D 2 and serotonin 5-HT 2 are relevant in this M range, this would make a selective disruption of NMDA transmission by these agents unlikely.…”

Section: Discussionmentioning

confidence: 99%

NMDA receptor antagonists ketamine and PCP have direct effects on the dopamine D2 and serotonin 5-HT2 receptors—implications for models of schizophrenia

2002

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“…The anesthetic potency of the S(+)-isomer is approximately three or four times that of the R(-)-isomer [1] . In vivo, there is a statistically significant (P<0.01) smaller clearance and volume of distribution for R(-)-ketamine compared with S(+)-ketamine [2] . Several animal studies have shown that the clearance and volume of distribution of ketamine are related to hepatic blood flow, which can be predicted in humans [3] .…”

Section: Pharmacokinetics (Pk) and Pharmacodynamics (Pd)mentioning

confidence: 91%

Ketamine use in current clinical practice

2016

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After nearly half a century on the market, ketamine still occupies a unique corner in the medical armamentarium of anesthesiologists or clinicians treating pain. Over the last two decades, much research has been conducted highlighting the drug's mechanisms of action, specifically those of its enantiomers. Nowadays, ketamine is also being utilized for pediatric pain control in emergency department, with its anti-hyperalgesic and anti-inflammatory effects being revealed in acute and chronic pain management. Recently, new insights have been gained on ketamine's potential anti-depressive and antisuicidal effects. This article provides an overview of the drug's pharmacokinetics and pharmacodynamics while also discussing the potential benefits and risks of ketamine administration in various clinical settings.

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Pharmacokinetics and Dynamics of Ketamine Enantiomers Using a Stereoselective Analytical Method

Cited by 30 publications

References 0 publications

Antinociceptive effects, metabolism and disposition of ketamine in ponies under target-controlled drug infusion

Antinociceptive effects, metabolism and disposition of ketamine in ponies under target-controlled drug infusion

NMDA receptor antagonists ketamine and PCP have direct effects on the dopamine D2 and serotonin 5-HT2 receptors—implications for models of schizophrenia

Ketamine use in current clinical practice

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