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.
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Br J Clin Pharmacol · Dec 2003
Randomized Controlled Trial Clinical TrialNo clinically significant pharmacokinetic interactions between voriconazole and indinavir in healthy volunteers.
Voriconazole is a new triazole antifungal agent, and is metabolized by the cytochrome P450 isoenzymes CYP2C9, CYP2C19 and to a lesser extent by CYP3A4. Protease inhibitors, such as indinavir, are also metabolized by cytochrome P450 (mainly CYP3A4). As these drugs are likely to be coadministered, these studies were performed to assess the pharmacokinetic interactions, safety and toleration of these drugs when taken together. ⋯ The coadministration of voriconazole and indinavir in healthy volunteers had no clinically significant effect on the pharmacokinetics of either voriconazole or indinavir.
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Br J Clin Pharmacol · Aug 2003
Randomized Controlled Trial Clinical TrialA simple pain model for the evaluation of analgesic effects of NSAIDs in healthy subjects.
Non-steroidal anti-inflammatory drugs (NSAIDs) are believed to counteract inflammation and inflammation-induced sensitization of nociceptors by inhibiting peripheral prostaglandin synthesis. We evaluated an experimental pain model for NSAIDs, that included an inflammatory component to mimic clinical inflammatory pain conditions. ⋯ The pain model we evaluated was well tolerated in all subjects and the effects of ibuprofen were highly significant. This model is simple, sensitive to NSAIDs' effects and therefore has potential for future experimental pain studies.
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Br J Clin Pharmacol · Jul 2003
Pharmacokinetics and clinical effects of phenytoin and fosphenytoin in children with severe malaria and status epilepticus.
Status epilepticus is common in children with severe falciparum malaria and is associated with poor outcome. Phenytoin is often used to control status epilepticus, but its water-soluble prodrug, fosphenytoin, may be more useful as it is easier to administer. We studied the pharmacokinetics and clinical effects of phenytoin and fosphenytoin sodium in children with severe falciparum malaria and status epilepticus. ⋯ Phenytoin and fosphenytoin administration at the currently recommended doses achieve plasma unbound phenytoin concentrations within the therapeutic range with few cardiovascular effects. Administration of fosphenytoin i.v. or i.m. offers a practical and convenient alternative to i.v. phenytoin. However, the inadequate control of status epilepticus despite rapid achievement of therapeutic unbound phenytoin concentrations warrants further investigation.