Clinical pharmacology : advances and applications
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In critically ill patients, monitoring free phenytoin concentration is a valuable method for phenytoin-dosage adjustment. However, due to technical difficulties and the high cost of these methods, the Sheiner-Tozer equation is routinely used for estimating free phenytoin concentration in clinical practice. There have been conflicting results concerning accuracy and precision of the Sheiner-Tozer equation for prediction of free phenytoin concentration in various patient populations. Therefore, this study was conducted to evaluate the accuracy and correlation of measured and calculated free phenytoin concentrations in neurointensive care patients with hypoalbuminemia. ⋯ Although there was a moderate correlation between calculated and measured free phenytoin concentration, the Sheiner-Tozer equation was not able to predict free phenytoin concentration accurately in all patients, especially in older patients. Therefore, monitoring free phenytoin serum concentration besides clinical outcomes should be considered for phenytoin-dose adjustment in critically ill patients.
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Detection of delirium in hospitalized patients remains challenging. The objective was to determine if the prescription of antipsychotic medications was associated with delirium. ⋯ Hospitalized patients who are acutely prescribed antipsychotics are likely to have delirium, but not all patients with delirium will be identified with this method. In health systems, utilization of the prescription of acute antipsychotics can be an efficient and specific method to identify delirious patients for targeted intervention.
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Carfilzomib, a selective proteasome inhibitor approved in the USA in 2012, is a single agent for relapsed and refractory multiple myeloma. Carfilzomib is administered as a 2-10-minute infusion on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle at a starting dose of 20 mg/m(2) for cycle 1 and a target dose of 27 mg/m(2) thereafter. In the pivotal Phase II study (PX-171-003-A1), carfilzomib 20/27 mg/m(2) provided durable responses in a heavily pretreated population with relapsed and refractory multiple myeloma (n=266), with an overall response rate of 22.9% and a median duration of response of 7.8 months. ⋯ New or worsening peripheral neuropathy was infrequent (13.9% overall, 1.3% grade 3, no grade 4). This review discusses findings of the integrated safety analysis and provides practical experience from a single institution in managing treatment-related and disease-related adverse events. Individualized treatment with proactive management of side effects and complications allows patients with advanced multiple myeloma to remain on carfilzomib for extended periods.
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In severe alcohol withdrawal (AW), benzodiazepines may be inadequate to control symptoms. In many situations, benzodiazepine dosing escalates despite no additional efficacy and introduces potential toxicities. Severe cases of AW may require additional agents to control symptoms. Case reports and studies have shown benefits with dexmedetomidine and propofol in severe AW, but these agents have not been compared with one another. This study compares the effects of dexmedetomidine and propofol on benzodiazepine and haloperidol utilization in patients with AW. ⋯ In patients with severe AW who require sedation, both dexmedetomidine and propofol have unique and advantageous properties. Both agents appear to have equivalent efficacy in reducing AW-related symptoms and benzodiazepine and haloperidol requirements. These results should be validated in a larger, prospective trial.
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Apixaban is an oral, selective, direct factor Xa inhibitor approved for thromboprophylaxis after orthopedic surgery and stroke prevention in patients with atrial fibrillation, and under development for treatment of venous thromboembolism. This study investigated the effect of a gastric acid suppressant, famotidine (a histamine H2-receptor antagonist), on the pharmacokinetics of apixaban in healthy subjects. ⋯ Famotidine does not affect the pharmacokinetics of apixaban, consistent with the physicochemical properties of apixaban (lack of an ionizable group and pH-independent solubility). Apixaban pharmacokinetics would not be affected by an increase in gastrointestinal pH due to underlying conditions (eg, achlorhydria), or by gastrointestinal pH-mediated effects of other histamine H2-receptor antagonists, antacids, or proton pump inhibitors. Given that famotidine is also an inhibitor of the human organic cation transporter (hOCT), these results indicate that apixaban pharmacokinetics are not influenced by hOCT uptake transporter inhibitors. Overall, these results support that apixaban can be administered without regard to coadministration of gastric acid modifiers.