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1. The purpose of the present study was to determine whether intracerebral microdialysis can be used for the assessment of local differences in drug concentrations within the brain. 2. Two transversal microdialysis probes were implanted in parallel into the frontal cortex of male Wistar rats, and used as a local infusion and detection device respectively.(More)
One major task in clinical pharmacology is to determine the pharmacokinetic-pharmacodynamic (PK-PD) parameters of a drug in a patient population. NONMEM is a program commonly used to build population PK-PD models, that is, models that characterize the relationship between a patient's PK-PD parameters and other patient specific covariates such as the(More)
BACKGROUND Thiopental produces a concentration-dependent continuum of effects on the cortical electroencephalogram (EEG) that has been linked to behavioral measures of anesthetic depth. The complexity of the response, however, limits a clear insight into the neurophysiologic actions of thiopental. The current study investigated thiopental actions on(More)
This study characterizes the pharmacokinetic-pharmacodynamic (PK-PD) relationships of the cardiovascular, EEG, hypnotic and ventilatory effects of the alpha-2 adrenergic agonist dexmedetomidine in rats. Dexmedetomidine was administered by a single rapid infusion (n = 6) and by an infusion regimen of gradually increasing rate (n = 8). HR, mean arterial(More)
The concentration EEG effect relationship of heptabarbital was modeled using effect parameters derived from aperiodic EEG analysis. Male Wistar rats (n = 10) received an intravenous infusion of heptabarbital at a rate of 6-9 mg/kg per min until burst suppression with isoelectric periods of 5 sec or longer. Arterial blood samples were obtained and EEG was(More)
Electroencephalogram (EEG) effect parameters may be useful in pharmacokinetic-pharmacodynamic modelling studies of drug effects on the central nervous system (CNS). Effect parameters derived from a quantitative analysis of the EEG appear to be perfectly suited to characterise the relationships between pharmacokinetics and pharmacodynamics of benzodiazepines(More)
The in vivo concentration-anticonvulsant effect relationships of six benzodiazepines, midazolam, clonazepam, oxazepam, flunitrazepam, diazepam and clobazam were quantified in individual rats and correlated with the affinity to the GABAA-benzodiazepine receptor complex. Furthermore the interaction between midazolam and the benzodiazepine antagonist(More)
This study characterizes the anesthetic profile of dexmedetomidine on the basis of steady-state plasma concentrations using defined stimulus-response, ventilatory, and continuous electroencephalographic (EEG) and cardiovascular effect measures in rats. At constant plasma concentrations of dexmedetomidine (range, 0.5-19 ng/ml), targeted and maintained by(More)
1. Concentration-effect relationships of midazolam were assessed in an open study in six healthy volunteers. Saccadic eye movements and EEG parameters derived by fast Fourier transform (FFT) and aperiodic analysis (AP) were used to quantify drug effects. 2. Midazolam was infused at a rate of 0.6 mg kg-1 h-1 for a maximum of 15 min. Hypnotic effects were(More)
The pharmacodynamic interaction between midazolam and its active metabolite ␣-OH-midazolam was investigated to evaluate whether estimates of relevant pharmacodynamic parameters are possible after administration of a mixture of the two. Rats were administered 10 mg/kg of midazolam, 15 mg/kg of ␣-OH-midazolam, or a combination of 3.6 mg/kg of midazolam and 35(More)