Methods: In a 5-phase randomized controlled trial of 16 healthy volunteers a 0.05 mg dose of repaglinide was administered alone and together with the Geneva cocktail, containing oral probe substrates for six CYP enzymes (50 mg caffeine/CYP1A2, 20 mg bupropion/CYP2B6, 10 mg flurbiprofen/CYP2C9, 10 mg omeprazole/CYP2C19, 10 mg dextromethorphan/CYP2D6 and 1 mg midazolam/CYP3A4), and the effects of clopidogrel and gemfibrozil on the cocktail including repaglinide were assessed. Venous blood samples were collected before the administration of the pretreatment drugs and 5 minutes before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 23 hours after the administration of the study drugs. Blood glucose values and adverse effects were monitored up to 12 hours. Standardized meals were served 1, 3, 7 and 9 hours after the administration of the study drugs. Concentrations of the probe substrates and their metabolites were quantitated with LC-MS/MS techniques.
Introduction: Renally impaired (RI) patients have an increased potential to accumulate dalteparin and consequently an increased risk of (major) bleeding events. To reduce this risk, guidelines advice dalteparin dose reduction with anti-Xa monitoring. However, clinical experience has shown that dalteparin has a minimal tendency to accumulate in RI patients.
Introduction: The doctors are forced to prescribe multicomponent drugs therapy for a long treatment period, when tuberculosis is due to the resistant strains of M. tuberculosis. The use of multicomponent drugs therapy is often followed by the high risks of adverse events. It demands the search of triggers and signals of adverse events for prospective minimization of risks by monitoring the drug prescribing quality.
Conclusions: According to our results, few ICSRs describing CLS have been collected in EV in front of billion administered doses. This could underline the rarity of this AEFI or the limit of underreporting of spontaneous reporting and therefore also our study. Since the significant clinical relevance of CLS, this AEFI requires a careful monitoring.
Conclusion: For glucarpidase there are no data that allow for an assessment of the relationship between exposure and efficacy of MTX conversion. As such the minimal effective dose is unknown. Based upon in vitro enzyme activity (1 unit of glucarpidase activity catalyses the hydrolysis of 1 μmol of MTX in 1 ml in 1 minute) the recommended dose seems to be more than sufficient even taking into account redistribution of MTX. Our patients were all treated with 1000 IE and time to MTX < 0,25 μmol/L was comparable between patients. MTX levels were measured by immunoassay which does not allow for distinction between DAMPA and MTX. Alternative approaches to monitor MTX levels after glucarpidase administration, such as HPLC, are required in order to better evaluate the effectiveness of glucarpidase at lower doses than recommended. Glucarpidase is an expensive drug. By limiting the dose to 1000 IE we required 20 vials less than otherwise required (savings 460.000 euros). 2b1af7f3a8