British journal of clinical pharmacology
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Br J Clin Pharmacol · Feb 2004
Randomized Controlled Trial Clinical TrialModelling acute tolerance to the EEG effect of two benzodiazepines.
We studied the development of acute tolerance to the EEG effect of midazolam and the new benzodiazepine Ro 48-6791. ⋯ Midzolam and Ro 48-6791 showed acute tolerance to the EEG effect which might be caused by competitive interaction with the metabolite.
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Br J Clin Pharmacol · Feb 2004
Randomized Controlled Trial Comparative Study Clinical TrialComparative population pharmacokinetics of lorazepam and midazolam during long-term continuous infusion in critically ill patients.
It is well established that there is a wide intra- and interindividual variability in dose requirements for lorazepam and midazolam in intensive care patients. The objective of this study was to compare the population pharmacokinetics of lorazepam and midazolam after long-term continuous infusion in mechanically ventilated critically ill patients. ⋯ The pharmacokinetics of both lorazepam and midazolam were well described by a two-compartment model. Inclusion of alcohol abuse and age as covariates improved both models. PEEP was identified as an additional covariate for lorazepam, and the APACHE score for midazolam. For both drugs there is a large interindividual variability in their pharmacokinetics when used for long-term sedation in critically ill patients. However, the intra-individual variability is much lower for lorazepam.