Clinical therapeutics
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Clinical therapeutics · Apr 2008
Randomized Controlled Trial Comparative StudyCombination therapy versus monotherapy as initial treatment for stage 2 hypertension: a prespecified subgroup analysis of a community-based, randomized, open-label trial.
Current guidelines suggest consideration of initial combination therapy for patients with stage 2 hypertension, but rates of hypertension treatment and control in clinical practice vary according to age, race, sex, and body mass index (BMI). ⋯ Across various subgroups of patients with stage 2 hypertension, combination therapy was consistently associated with a significantly greater reduction in SBP than monotherapy. With the exception of a significantly greater increase in dizziness compared with monotherapy, combination therapy was well tolerated.
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Clinical therapeutics · Apr 2008
Randomized Controlled Trial Multicenter Study Comparative StudyEffects of carvedilol on left ventricular function and oxidative stress in infants and children with idiopathic dilated cardiomyopathy: a 12-month, two-center, open-label study.
This study was conducted to determine the effects of carvedilol adjunct to standard treatment on left ventricular function (LVF), estimated as ejection fraction (EF) and fractional shortening (FS) on echocardiography, in children with idiopathic dilated cardiomyopathy (DCM). A secondary end point was to characterize the antioxidant potential of carvedilol. ⋯ These pediatric patients with DCM treated for 12 months with carvedilol (up to 0.8 mg/kg/d in children
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Clinical therapeutics · Apr 2008
Randomized Controlled Trial Comparative StudyPharmacokinetics of single-dose and multiple-dose memantine in healthy chinese volunteers using an analytic method of liquid chromatography-tandem mass spectrometry.
This study consisted of 2 phases: development of a liquid chromatography-tandem mass spectrometry (LC/MS) method for determination of memantine in human plasma and characterization of single-dose and multiple-dose pharmacokinetic profiles of memantine in healthy Chinese volunteers using the LC/MS method. ⋯ In these healthy Chinese subjects, the t(1/2) and MRT values were fixed and did not increase following the increased dose, and the AUC(infinity) and C(max) values increased following the increasing dosage of memantine. Linear pharmacokinetics was found at doses from 5 to 20 mg. The multiple-dose pharmacokinetic parameters (other than C(max)) were nearly similar compared with the single-dose administration. The maximum plasma concentration of memantine after multiple-dose administration was greater than that after a single-dose administration, suggesting memantine accumulation with multiple-dose administration of 5 mg and requiring further confirmation in larger studies.
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Clinical therapeutics · Apr 2008
Randomized Controlled Trial Multicenter Study Comparative StudyHospital resource utilization with doripenem versus imipenem in the treatment of ventilator-associated pneumonia.
Ventilator-associated pneumonia (VAP) is a common nosocomial infection that is associated with prolonged length of stay (LOS) and significant mortality. ⋯ Of the 3 primary end points in this analysis, hospital LOS and time on mechanical ventilation were significantly shorter with doripenem compared with imipenem; no statistical significance was observed in ICU LOS. These findings suggest that doripenem use may be associated with an economic and clinical benefit to patients and hospitals.
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Clinical therapeutics · Apr 2008
Randomized Controlled Trial Comparative StudyCurrent target ranges of mycophenolic acid exposure and drug-related adverse events: a 5-year, open-label, prospective, clinical follow-up study in renal allograft recipients.
Two recent randomized clinical trials--Fixed Dose Versus Concentration Controlled and the Apomygre--evaluating the benefit of therapeutic drug monitoring of mycophenolate mofetil (MMF) in renal allograft recipients reported conflicting results. In both studies, target mycophenolic acid (MPA) AUC(0-12 h) ranges (ie, values used to guide MMF dosing) were derived from a previous study establishing target MPA AUC(0-12 h) ranges in cyclosporine-treated patients between 30 and 60 mg/L x h(-1). Both studies found an association between MPA exposure and acute rejection. However, only one of the studies found concentration-controlled MMF dosing to be significantly associated with less biopsy-proven acute-rejection episodes compared with fixed dosing. No reduced incidence of MMF-related adverse events (AEs) was observed in either of the 2 trials when MMF concentration-controlled and fixed dosing were compared. ⋯ Renal allograft recipients suffering from leukopenia or anemia related to MMF could potentially benefit, at least in part, from MMFdose adjustments based on target therapeutic MPA AUC(0-12 h) ranges between 30 and 60 mg/L x h(-1). This study did not find these target MPA AUC(0-12 h) ranges to be of clinical utility in guiding MMF dosing in patients with gastrointestinal or infectious AEs. Larger prospective studies are necessary to examine the risk for MPA underexposure in patients carrying the UGTIA9 T-275A and/or C-2152T SNP.