Int J Clin Pharm Th
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Int J Clin Pharm Th · Nov 2012
Randomized Controlled Trial Comparative StudyTolerability, pharmacokinetics, and pharmacodynamics of the glucokinase activator AZD1656, after single ascending doses in healthy subjects during euglycemic clamp.
AZD1656 is a novel glucokinase activator with a postulated dual mechanism of action by activating glucokinase in both the pancreas and the liver, and with the potential to deliver effective glucose-lowering in Type 2 diabetes mellitus. Here, we present the tolerability, pharmacokinetics and pharmacodynamics of AZD1656 in two single-blind, randomized, placebo-controlled studies, one with Western and the other with Japanese healthy adult male subjects. ⋯ No safety concerns were raised. AZD1656 displayed uncomplicated pharmacokinetics and dose-dependent pharmacodynamics effects were observed. The results suggest no ethnic differences in AZD1656 tolerability, pharmacokinetics or pharmacodynamics.
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Int J Clin Pharm Th · Nov 2012
Prediction of distribution volume of vancomycin in critically ill patients using extravascular lung water and pulmonary vascular permeability indices.
Alterations in distribution volume affect the concentrations of hydrophilic drugs in plasma and tissues at the time of initial therapy. When the distribution volume of hydrophilic antimicrobials is increased in critically ill patients with a serious infection, antimicrobial concentrations are reduced, which may adversely affect the efficacy of antimicrobial therapy. A transpulmonary thermodilution technique system (PiCCO) enables measurements of pulmonary vascular permeability index (PVPI) and extravascular lung water index (EVLWI), which are related to pulmonary edema and pulmonary vascular permeability, respectively. In addition, those indices may also be related to the distribution volume of hydrophilic antimicrobials. The aim of this study was to investigate the relationships of PVPI and EVLWI with the distribution volume of vancomycin (Vss), as well as to establish a method for estimating Vss for planning an appropriate initial dose for individual patients. ⋯ EVLWI determined by the PiCCO system is useful to predict Vss and should lead to more effective vancomycin therapy for critically ill patients at the initial stage.
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Int J Clin Pharm Th · Nov 2012
Randomized Controlled Trial Comparative StudyEffects of 90-day hypolipidemic treatment on insulin resistance, adipokines and proinflammatory cytokines in patients with mixed hyperlipidemia and impaired fasting glucose.
Concerns regarding worsening insulin sensitivity associated with statin treatment have recently emerged. Therefore the aim of this study was to assess and compare the effects of 90-day monotherapies with fenofibrate and atorvastatin, as well as combined therapy, on fasting plasma glucose, insulin resistance index, adipokines (leptin, resistin, adiponectin) and levels of proinflammatory cytokines (TNF-α, IL-6) in patients with impaired fasting glucose (IFG) and mixed hyperlipidemia. ⋯ Fenofibrate-based treatment was associated with improved insulin sensitivity. Atorvastatin did not cause a deterioration in insulin sensitivity. Hypolipidemic therapies resulted in significant changes in the proinflammatory cytokine network as well as in adipokine levels. At the end of the study the measured parameters nearly resembled those of the healthy subjects.