European journal of clinical pharmacology
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Eur. J. Clin. Pharmacol. · Apr 2000
Randomized Controlled Trial Clinical TrialPharmacokinetics and pharmacodynamics of propofol 6% SAZN versus propofol 1% SAZN and Diprivan-10 for short-term sedation following coronary artery bypass surgery.
A new formulation of propofol 6% in Lipofundin MCT/LCT 10% (propofol 6% SAZN) has been developed in order to reduce the fat, emulsifier and volume load that is given during prolonged infusions of propofol. The pharmacokinetics, pharmacodynamics and safety characteristics of propofol 6% SAZN were investigated during a short-term infusion and compared with the commercially available product propofol 1% in Intralipid 10% (Diprivan-10) and propofol 1% in Lipofundin MCT/LCT 10% (propofol 1% SAZN). ⋯ The pharmacokinetics, pharmacodynamics and safety characteristics of propofol 6% SAZN are in good agreement with those of the 1% formulations. Propofol 6% SAZN therefore provides a useful alternative to the commercially available 1% formulation for short-term sedation in the intensive care unit. Expected advantages in long-term sedation of the 6% over 1% formulation are the subject of an ongoing study.
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Eur. J. Clin. Pharmacol. · Feb 2000
Randomized Controlled Trial Clinical TrialHaemodynamic interactions between the novel calcium sensitiser levosimendan and isosorbide-5-mononitrate in healthy subjects.
The new calcium sensitiser levosimendan also possesses vasodilatory effects due to potassium-channel opening. The aim of the present study was to assess the possible haemodynamic interactions between levosimendan and isosorbide-5-mononitrate in young healthy men. ⋯ No major additive haemodynamic effects of the combination of levosimendan and isosorbide-5-mononitrate compared with each drug alone could be observed at rest. However, during an orthostatic test, the circulatory response was significantly potentiated with the combination, and three of the subjects were unable to stand upright for the stipulated time.
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Eur. J. Clin. Pharmacol. · Feb 2000
Randomized Controlled Trial Clinical TrialHuman halothane metabolism, lipid peroxidation, and cytochromes P(450)2A6 and P(450)3A4.
Halothane undergoes both oxidative and reductive metabolism by cytochrome P450 (CYP), respectively causing rare immune-mediated hepatic necrosis and common, mild subclinical hepatic toxicity. Halothane also causes lipid peroxidation in rodents in vitro and in vivo, but in vivo effects in humans are unknown. In vitro investigations have identified a role for human CYPs 2E1 and 2A6 in oxidation and CYPs 2A6 and 3A4 in reduction. The mechanism-based CYP2E1 inhibitor disulfiram diminished human halothane oxidation in vivo. This investigation tested the hypotheses that halothane causes lipid peroxidation in humans in vivo, and that CYP2A6 or CYP3A4 inhibition can diminish halothane metabolism. ⋯ These results provide the first evidence for halothane-dependent lipid peroxidation in humans. Methoxsalen effects on halothane oxidation confirm in vitro results and suggest limited CYP2A6 participation in vivo. CYP2A6-mediated, like CYP2E1-mediated human halothane oxidation, can be inhibited in vivo by mechanism-based CYP inhibitors. In contrast, clinical halothane reduction and lipid peroxidation were not amenable to suppression by CYP inhibitors.
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Eur. J. Clin. Pharmacol. · Jan 2000
Start of oral morphine to cancer patients: effective serum morphine concentrations and contribution from morphine-6-glucuronide to the analgesia produced by morphine.
To investigate the serum concentrations of morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) and the relationships between serum concentrations and clinical effects associated with start of morphine treatment in cancer patients. ⋯ In this study, a mean serum trough morphine concentration of 66 nmol/l was associated with satisfactory pain relief when disease progression required an increase in intensity of pain therapy from step II to step III in the World Health Organization pain ladder. An increased ratio of M6G to morphine serum concentrations predicted lower effective serum morphine concentrations at the time of satisfactory pain relief. This observation supports that M6G contributes to the pain control produced by oral morphine in patients with pain caused by malignant disease.
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Eur. J. Clin. Pharmacol. · Nov 1999
Randomized Controlled Trial Clinical TrialAssessment of the efficacy and safety of paracetamol, ibuprofen and nimesulide in children with upper respiratory tract infections.
The aim of this study was to assess and compare the efficacy and tolerability of paracetamol, ibuprofen and nimesulide in children with upper respiratory tract infections (URTIs). ⋯ The results of this study demonstrated that the anti-pyretic effectiveness of nimesulide is better than paracetamol and ibuprofen in febrile children with URTIs. However, new studies in larger paediatric populations are required to explore the anti-inflammatory effect of nimesulide.