Comparative Pharmacology of the Ketamine Isomers

Abstract

The clinical and electroencephalographic (EEG) effects of the individual ketamine isomers were compared with the racemic mixture in five volunteers who received each drug on a separate occasion. Racemic ketamine 275 +/- 25 mg, s(+) ketamine 140 +/- 21 mg or R(-) ketamine 429 +/- 37 mg produced an anaesthetic state lasting 6 +/- 2 min (mean +/- SD). However, the EEG evaluation of the R(-) isomer revealed less overall slowing, and an absence of the large slow wave complexes produced by the S(+) isomer and the racemic mixture. The pharmacokinetic profiles for the individual isomers of ketamine did not differ significantly from the racemic mixture. Even though the apparent anaesthetic state produced in these healthy volunteers did not differ qualitatively between the three drug groups, recovery times (assessed using a standardized battery of psychometric tests) were consistently shorter following the individual isomers compared with the racemic mixture. The serum ketamine concentrations associated with regaining consciousness and orientation were consistent with an S(+):R(-) isomer potency ratio of 4:1. In terms of their ability to impair psychomotor function, the S(+):R(-) potency ratio varied from 3:1 to 5:1. After comparable degrees of CNS depression, we conclude that the more potent S(+) isomer of ketamine was associated with a more rapid recovery of psychomotor skills than the currently used racemic mixture.

High-dose S(+)- ketamine improves neurological outcome following incomplete cerebral ischemia in rats

“…There is also more rapid recovery of psychomotor function and performance. [3][4][5] Studies in laboratory animals have shown that racemic ketamine exhibits some neuroprotective potential when infused prior to incomplete cerebral ischemia or following traumatic brain injury. [6][7][8][9] For example, studies in this animal model of incomplete hemispheric ischemia have shown that neurological outcome was improved at three days from insult with racemic ketamine.…”

Total intravenous anaesthesia with propofol-racemic ketamine and propofol-S-ketamine: a comparative study and haemodynamic evaluation in dogs undergoing ovariohysterectomy

“…We asked if the benefits of S(+)ketamine reported for other species (Ryder et al 1978, White et al 1985, Pfenninger et al 2002, Strümper et al 2004 regarding its clinically apparent potency, overall quality of anesthesia and decreased undesirable effects, would have a synergistic effect when associated to propofol. Premedications as well as different degrees of surgical stimulus and the concurrent use of other drugs may complicate comparison of different anaesthetic drugs both at combined administration.…”

“…In man, S(+)Ketamine has an anaesthetic-analgesic effect two to four times greater than racemic ketamine (White et al 1985;Mathisen et al 1995;Lauretti et al 2000), and its hyptonic effect is more potent than that of the R(-) isomer (Terra et al 1999), allowing the use of lower doses of S(+) ketamine compared to racemic ketamine.…”

Erratum to: Intranasal administration of medication for children in emergency services

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In der zunächst veröffentlichten OnlineVersion des Beitrags wurden falsche Angaben zur Dosierung von S-Ketamin gemacht.Ketamin und das verwandte S-Ketamin können beide intranasal mittels MAD-Device verabreicht werden.Verschiedenste Studien belegen, dass S-Ketamin verglichen zu Ketamin-Razemat in halber Dosierung einen äquivalen-ten Effekt aufweist [1,2,3]. Aus dieser Tatsache heraus sollte auch bei der intranasalen Applikation zunächst mal die halbe Dosierung verabreicht werden.

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“…Verschiedenste Studien belegen, dass S-Ketamin verglichen zu Ketamin-Razemat in halber Dosierung einen äquivalen-ten Effekt aufweist [1,2,3]. Aus dieser Tatsache heraus sollte auch bei der intranasalen Applikation zunächst mal die halbe Dosierung verabreicht werden.…”