Clinical therapeutics
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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.
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Clinical therapeutics · Mar 2008
Randomized Controlled Trial Multicenter StudyPharmacokinetic, pharmacodynamic, and tolerability profiles of the dipeptidyl peptidase-4 inhibitor alogliptin: a randomized, double-blind, placebo-controlled, multiple-dose study in adult patients with type 2 diabetes.
Alogliptin is a highly selective dipeptidyl peptidase-4 (DPP-4) inhibitor that is under development for the treatment of type 2 diabetes (T2D). ⋯ In these adult patients with T2D, alogliptin inhibited plasma DPP-4 activity and significantly decreased PPG levels. The PK and PD profiles of multiple doses of alogliptin in this study supported use of a once-daily dosing regimen. Alogliptin was generally well tolerated, with no dose-limiting toxicity.
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Clinical therapeutics · Mar 2008
Randomized Controlled Trial Comparative Study Clinical TrialPharmacokinetics, efficacy, and tolerability of fentanyl following intranasal versus intravenous administration in adults undergoing third-molar extraction: a randomized, double-blind, double-dummy, two-way, crossover study.
The aim of this study was to compare the pharmacokinetic profile, as well as the efficacy and tolerability, of i.n. and i.v. administration of fentanyl in acute, episodic pain in patients undergoing third-molar extraction. ⋯ Onsets and durations of analgesia were not significantly different between single doses of i.n. and i.v. fentanyl in these adults undergoing third-molar extraction. Both i.n. and i.v. administration were generally well tolerated.
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Clinical therapeutics · Mar 2008
ReviewClinical and patient-reported outcomes in clinical trials of abatacept in the treatment of rheumatoid arthritis.
Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic joint inflammation, which if left untreated leads to progressive disability and joint destruction. A combination of antiinflammatory agents, steroids, disease-modifying antirheumatic drugs, and biological agents are used to treat RA. Beyond the use of conventional measures of disease activity, such as American College of Rheumatology (ACR) response rates, the importance of patient-reported outcomes (PROs) in assessing therapeutic benefits is gaining increasing emphasis in clinical trials of RA and other chronic illnesses. Clinical trials testing new RA therapeutics generally include health-related quality of life (HRQoL) measures and assessments of function and disability. Abatacept, a costimulation modulator that selectively targets the activation of T cells and downregulates the immune response, has been approved by the US Food and Drug Administration for the treatment of RA, with or without methotrexate. ⋯ These 6 published trials found that abatacept was associated with significant improvements in both conventional measures of disease activity and PROs. Continued assessment of these outcomes will be required to further support the findings of the Phase II and III abatacept clinical trial literature reviewed here.