European journal of clinical pharmacology
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Eur. J. Clin. Pharmacol. · Jun 2001
ReviewMicrodialysis. A novel tool for clinical studies of anti-infective agents.
In vivo microdialysis (MD) is an innovative clinical technique that has been employed in preclinical research and metabolic studies in patients for more than a decade. Recently, MD has been adopted for human drug studies and has opened up the opportunity to quantify tissue drug distribution in vivo. The particular advantage of MD for the anti-infective field relates to the fact that MD allows for online measurement of the unbound, pharmacologically active drug fraction in the interstitial space fluid (ISF), the anatomically defined target site for most bacterial infections. ⋯ It will be shown that MD has become feasible in most human tissues including brain and lung. So far, several MD studies have demonstrated that anti-microbial concentrations at the effect site may be subinhibitory, although effective concentrations are attained in serum, a finding that has significant impact on clinical decision making. In addition to its property as a pharmacokinetic sampling technique, MD offers unique opportunities in pharmacokinetic-pharmacodynamic (PK-PD) research and has the potential to streamline the decision process on proper drug dosing in drug development.
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Eur. J. Clin. Pharmacol. · May 2001
An optimized methodology for combined phenotyping and genotyping on CYP2D6 and CYP2C19.
A method for simultaneous phenotyping and genotyping for CYP2D6 and CYP2C19 was tested. Six healthy volunteers were selected (three extensive and three poor metabolisers for CYP2D6). CYP2D6 was probed with dextromethorphan and metoprolol and CYP2C19 was probed with omeprazole. ⋯ The correlation between the metabolic ratio based on timed individual measurements and the metabolic ratio based on the AUC0-12 values was significant at 3 h post-dose for all probes. In conclusion, the following procedure is suggested: administer metoprolol (100 mg) and omeprazole (40 mg); after 3 h, take a blood sample to assess the genotype and the metabolic ratio for CYP2D6 (metoprolol over alpha-hydroxymetoprolol) and CYP2C19 (omeprazole over 5-hydroxyomeprazole) in plasma. With this procedure, all necessary information on the individual CYP2D6 and CYP2C19 metabolising capacity can be obtained in a practical, single-sample approach.
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Eur. J. Clin. Pharmacol. · Apr 2001
The effect of community-acquired pneumonia on plasma esterases in older people.
Pneumonia is a major cause of morbidity and mortality in older people. The poor outcome of older pneumonia patients despite treatment is still not understood. ⋯ The activities of several esterases are reduced in older pneumonia patients. Other enzymes including aspirin esterase and induced monocyte AHH activity are unaltered in pneumonia. There was a significant inverse relationship between the activities of all esterases studied and the British Thoracic Society pneumonia poor prognostic index.
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Eur. J. Clin. Pharmacol. · Jan 2001
Randomized Controlled Trial Clinical TrialSalmeterol and fluticasone propionate given as a combination. Lack of systemic pharmacodynamic and pharmacokinetic interactions.
To investigate the potential for systemic pharmacodynamic and pharmacokinetic interactions between inhaled salmeterol and fluticasone propionate when repeat doses of the two drugs are given in combination to healthy subjects. ⋯ These results in healthy subjects indicate that there is no systemic pharmacodynamic or pharmacokinetic interaction between inhaled salmeterol and fluticasone propionate when given in combination.
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Eur. J. Clin. Pharmacol. · Dec 2000
Clinical TrialInfluence of continuous veno-venous haemodiafiltration and continuous veno-venous haemofiltration on the pharmacokinetics of fluconazole.
To compare the elimination of fluconazole by continuous veno-venous haemodiafiltration (CVVHD) and continuous veno-venous haemofiltration (CVVH) at different dosages. ⋯ A daily dosage of 400-800 mg fluconazole is recommended in the treatment of life-threatening fungal infections in critically ill patients undergoing CVVHD since the clearance of CVVHD may considerably exceed the clearance in patients with normal renal function, which is about 20 ml/min. Drug monitoring is highly recommended for these patients.