Abstract | BACKGROUND: METHODS: In 12 healthy male volunteers the effect of rifampicin versus placebo pretreatment on S-ketamine-induced analgesia and cognition was quantified; the S-ketamine dosage was 20 mg/h for 2 h. The relative ketamine and norketamine contribution to effect was estimated using a linear additive population pharmacokinetic-pharmacodynamic model. RESULTS:
S-ketamine produced significant analgesia, psychotropic effects ( drug high), and cognitive impairment (including memory impairment and reduced psychomotor speed, reaction time, and cognitive flexibility). Modeling revealed a negative contribution of S- norketamine to S-ketamine- induced analgesia and absence of contribution to cognitive impairment. At ketamine and norketamine effect concentrations of 100 ng/ml and 50 ng/ml, respectively, the ketamine contribution to analgesia is -3.8 cm (visual analog pain score) versus a contribution of norketamine of +1.5 cm, causing an overall effect of -2.3 cm. The blood-effect site equilibration half-life ranged from 0 (cognitive flexibility) to 11.8 ( pain intensity) min and was 6.1 min averaged across all endpoints. CONCLUSIONS:
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Authors | Erik Olofsen, Ingeborg Noppers, Marieke Niesters, Evan Kharasch, Leon Aarts, Elise Sarton, Albert Dahan |
Journal | Anesthesiology
(Anesthesiology)
Vol. 117
Issue 2
Pg. 353-64
(Aug 2012)
ISSN: 1528-1175 [Electronic] United States |
PMID | 22692377
(Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Analgesics
- Ketamine
- norketamine
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Topics |
- Acute Pain
(drug therapy)
- Adolescent
- Adult
- Analgesics
(pharmacology)
- Cognition
(drug effects)
- Hot Temperature
- Humans
- Ketamine
(analogs & derivatives, pharmacology)
- Male
- Memory
(drug effects)
- Pain Management
(methods, statistics & numerical data)
- Pain Measurement
(methods, statistics & numerical data)
- Psychomotor Performance
(drug effects)
- Reaction Time
(drug effects)
- Reference Values
- Single-Blind Method
- Young Adult
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