Kinetics

Publication Title: 
Biochemical Pharmacology
Author(s): 
Morita, K.
Yamamoto, I.
Iwata, H.
Publication Title: 
The Journal of Pharmacology and Experimental Therapeutics

Four pharmacologic actions of intravenous ketamine (30 mg/kg) were studied in the rat. To elucidate the mechanism(s) terminating the pharmacologic effects, animals were pretreated with ketamine and agents anticipated to modify hepatic microsomal metabolism, including phenobarbital and SKF 525A.

Author(s): 
Marietta, M. P.
White, P. F.
Pudwill, C. R.
Way, W. L.
Trevor, A. J.
Publication Title: 
The Journal of Pharmacology and Experimental Therapeutics

The pharmacokinetics of sodium-gamma-hydroxybutyrate (NaGHB) have been examined as functions of dose and route of administration. The elimination of NaGHB appeared to be controlled by a capacity-limited process which can be described by Michaelis-Menten kinetics.

Author(s): 
Lettieri, J. T.
Fung, H. L.
Publication Title: 
The Journal of Pharmacology and Experimental Therapeutics

Circadian rhythms in the response to ethanol were investigated in male, Swiss-Webster mice. Significant circadian variations were observed in increased and decreased spontaneous locomotor activity induced by ethanol (2 or 4 mg/g i.p., respectively) and in the hypothermic response to ethanol with the greatest effect generally occurring during the dark phase of the 12 hr:12 hr. light-dark cycle when the normal activity of the animals was highest. Ethanol was also more lethal during the dark phases as compared to the light phase.

Author(s): 
Deimling, M. J.
Schnell, R. C.
Publication Title: 
Neuroscience Letters

The rates of local cerebral glucose utilization have been measured in normal conscious and hypnotized rabbits by the [14C]deoxyglucose method. In control rabbits the rates vary widely throughout the brain, with the values in gray matter broadly distributed around an average which is about 3 times greater than that of white matter. The higher values area in structures of auditory system (superior olive, inferior colliculus, auditory cortex).

Author(s): 
Passero, S.
Carli, G.
Battistini, N.
Publication Title: 
British Journal of Anaesthesia

Etomidate was injected i.v. within 10 or 60 s at various doses. After etomidate 0.3 mg kg-1 the plasma concentration was 1.6 micrograms ml-1 at 1 min after the end of injection. For about 7 min a good hypnotic effect (stages C0-D2) was observed on the e.e.g. recording. For surgical procedures, however, a combination with analgesic drugs appeared to be necessary. When the dose of etomidate was increased (0.1-0.4 mg kg-1) a linear increase in plasma concentration and slow e.e.g. activity was observed concomitantly.

Author(s): 
Doenicke, A.
Löffler, B.
Kugler, J.
Suttmann, H.
Grote, B.
Publication Title: 
Experientia
Author(s): 
Schnell, R. C.
Early, J. L.
Publication Title: 
Pharmacology, Biochemistry, and Behavior

Pretreatment of mice with prostaglandin synthetase inhibitors (PGSI's) antagonizes alcohol-induced behaviors. This study examined genetic and time course factors of this effect and studied the effects of a putative prostaglandin antagonist (SC-19220) on ethanol sleep time. Long Sleep (LS) and Short Sleep (SS) mice, lines bred for differential response to an hypnotic dose of ethanol, showed a four-fold difference in their dose-response curves for indomethacin antagonism of ethanol-induced hypnosis. Females of both lines required higher amounts of indomethacin relative to males.

Author(s): 
George, F. R.
Howerton, T. C.
Elmer, G. I.
Collins, A. C.
Publication Title: 
Anesthesia and Analgesia

An etomidate infusion regimen for hypnosis as part of balanced, totally intravenous anesthesia was designed to maintain plasma etomidate concentrations above the awakening concentration of 300 ng/ml while avoiding dose-related side effects. The etomidate infusion regimen of 0.1 mg/kg/min for 3 min, 0.02 mg/kg/min for 27 min, and 0.01 mg/kg/min for the remainder of the anesthesia was used together with intravenous bolus doses of fentanyl, droperidol, and pancuronium. This was evaluated in 11 patients and the kinetics of etomidate were reexamined.

Author(s): 
Fragen, R. J.
Avram, M. J.
Henthorn, T. K.
Caldwell, N. J.
Publication Title: 
Pharmacotherapy

Currently available anesthetic induction agents provide adequate hypnosis but are not ideal, particularly in the high risk patient (ASA class III-V), because most cause myocardial and/or respiratory depression and some have other important side effects. Etomidate was recently marketed as an intravenous anesthetic induction agent. It is a non-barbiturate hypnotic without analgesic properties that has less cardiovascular and respiratory depressant actions than sodium thiopental, even in patients with minimal cardiovascular reserve.

Author(s): 
Giese, J. L.
Stanley, T. H.

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