Int J Clin Pharm Th
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Int J Clin Pharm Th · May 2014
Randomized Controlled TrialEffect of dual bronchodilation with QVA149 on cardiac safety in healthy volunteers.
QVA149 is a dual bronchodilator, containing a fixed-dose combination of the long-acting β2-agonist indacaterol and long-acting muscarinic antagonist glycopyrronium, for the treatment of chronic obstructive pulmonary disease (COPD). Here we assess the potential of QVA149 (440/200 μg) at 4-fold the therapeutic dose for causing cardiac pharmacodynamic (PD) effects. ⋯ Overall, short-term administration of QVA149 showed a good cardiovascular safety and tolerability profile in healthy subjects.
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Int J Clin Pharm Th · Mar 2014
Randomized Controlled TrialEffects of sugammadex on activated partial thromboplastin time and prothrombin time in healthy subjects.
To assess the impact of sugammadex on activated partial thromboplastin time (APTT) and international normalized ratio for prothrombin time (PT(INR)) in healthy subjects and characterize the concentration-dependency of sugammadex effects on APTT and prothrombin time (PT) in normal human plasma in vitro. ⋯ Administration of sugammadex is associated with a dose-related, limited and transient prolongation of APTT and PT(INR) that is unlikely to be of clinical relevance.
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Int J Clin Pharm Th · Feb 2014
Randomized Controlled TrialBioequivalence assessment of two transdermal delivery systems of fentanyl in healthy Chinese volunteers.
The objective of this study was to investigate the bioequivalence of two formulations (generic preparation and Durogesic patch) of 4.2 mg fentanyl. They were assessed in relative bioavailability in 20 healthy Chinese male volunteers according to a single dose, 2-sequence, crossover randomized design. The two formulations were administered at two treatment days, separated by a washout period of 14 days. ⋯ ANOVA and two one-sided t-test procedures showed no significant difference in log-transformed Cmax, AUC0-T and AUC0-∞ while the 90% confidence interval (CI) of the ratio of the geometric means of their values were also used to assess bioequivalence between the two formulations. Based on these statistical inferences it was concluded that the two formulations exhibited comparable pharmacokinetic profiles and that test formulation is bioequivalent to reference formulation. The point estimate (90% CI) of two formulations was: AUC0-T, 96.7% (85 - 105%); AUC0-∞, 97.5% (89 - 110%); Cmax, 96.2% (91 - 104%); tmax, 97.1% (93 - 101%), respectively.
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Int J Clin Pharm Th · Feb 2014
Randomized Controlled TrialCorrelation of genotype, phenotype, and mRNA expression of CYP2D6 and CYP2C19 in peripheral blood leukocytes (PBLs).
The genetic polymorphism of drug metabolizing enzymes of the cytochrome P450 (CYP) families, especially CYP2D6 and CYP2C19, is the most important cause of variable responses of many drugs. Enzyme activity ranges from complete deficiency, so called poor metabolizers (PMs), to an ultrafast metabolism. While PMs and extensive metabolizers (EMs) can be well distinguished by genotyping, phenotyping is necessary to subdivide EMs from intermediate metabolizers (IMs). The aim of the study was to evaluate if messenger RNA (mRNA) concentration for CYP-enzymes in peripheral blood leukocytes (PBLs) will be predictive of systemic enzyme activity, allowing an easy and safe determination of metabolic activity. ⋯ The results do not support the concept of using mRNA expression profiles for CYP2D6 and CYP2C19 enzymes in PBLs for prediction of systemic enzyme activity.
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Int J Clin Pharm Th · Dec 2013
Randomized Controlled TrialNo clinically relevant interaction between sugammadex and aspirin on platelet aggregation and coagulation parameters.
This study evaluated interaction potential between sugammadex and aspirin on platelet aggregation. ⋯ There was no clinically relevant reduction in platelet aggregation with addition of sugammadex 4 mg/kg to aspirin. Pre-determined non-inferiority margins were not exceeded for bleeding time and APTT.