Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Dec 1995
Topographic electroencephalogram of propofol-induced conscious sedation.
To determine the effects of increasing doses of propofol that induce conscious sedation on the topographic electroencephalogram (EEG) of human volunteers and to test the hypothesis that more frontal brain areas are affected by low doses of propofol. ⋯ Topographic brain EEG mapping techniques indicate that frontal brain beta 1 EEG activity may be useful as an objective brain index of propofol conscious sedation.
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Clin. Pharmacol. Ther. · Dec 1995
Ceftazidime pharmacokinetics in preterm infants: effects of renal function and gestational age.
The objectives of this study were (1) to determine the effects of gestational age on ceftazidime pharmacokinetics in the preterm infant, (2) to relate these effects to changes in glomerular filtration rate (GFR), and (3) to establish appropriate dosage recommendations for preterm infants on day 3 of life. ⋯ Dosage recommendations for ceftazidime administration in preterm infants during the first week of life should be based on gestational age and GFR. Additional adjustments in dosage are indicated in preterm infants who are exposed prenatally to indomethacin.
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Clin. Pharmacol. Ther. · Nov 1995
Clinical TrialPharmacodynamic modeling of the electroencephalographic effects of flumazenil in healthy volunteers sedated with midazolam.
The purpose of this study was to model pharmacodynamically the reversal of midazolam sedation with flumazenil. Ten human volunteers underwent four different sessions. In session 1, individual midazolam pharmacokinetics and electroencephalographic pharmacodynamics were determined. ⋯ For a light sedation level, with a mean midazolam plasma concentration of 160 +/- 64 ng/ml, the mean half-life of the equilibration rate constant of flumazenil reversal is 5.0 +/- 2.5 minutes, and the mean effect site concentration causing 50% of Emax is 13.7 +/- 5.8 ng/ml. For a deep level of sedation, with a mean midazolam plasma concentration of 551 +/- 196 ng/ml, the mean half-life of the equilibration rate constant is 3.9 +/- 1.5 minutes, and the mean effect site concentration causing 50% of Emax is 20.6 +/- 6.8 ng/ml. This study provides an estimate of the magnitude of the blood/central nervous system equilibration delay for flumazenil antagonism of midazolam sedation and further defines the usefulness of the electroencephalogram as a measure of midazolam pharmacodynamic effect.
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Clin. Pharmacol. Ther. · Aug 1995
Randomized Controlled Trial Clinical TrialCentral nervous system effects of subdissociative doses of (S)-ketamine are related to plasma and brain concentrations measured with positron emission tomography in healthy volunteers.
Plasma concentrations, maximum regional brain concentrations, and specific regional binding in the brain after administration of 0, 0.1, and 0.2 mg/kg doses of (S)-ketamine were measured in a randomized, double-blind, crossover study in five volunteers and were related to induced effects such as analgesia, amnesia, and mood changes. Specific binding in the brain was assessed by simultaneous administration of (S)-[N-methyl-11C]ketamine quantified by positron emission tomography. ⋯ Memory impairment and psychotomimetic effects were related to dose, plasma concentration 4 minutes after administration, and decreased regional binding of (S)-ketamine in the brain and were consistently seen at plasma and maximum regional brain (S)-ketamine concentrations higher than 70 and 500 ng/ml, respectively. The magnitude of specific binding of (S)-ketamine, measured with positron emission tomography, can be related directly to drug effects.