Clinical therapeutics
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Clinical therapeutics · May 2008
Randomized Controlled Trial Multicenter Study Comparative StudyEfficacy and safety profiles of a new S(-)-amlodipine nicotinate formulation versus racemic amlodipine besylate in adult Korean patients with mild to moderate hypertension: an 8-week, multicenter, randomized, double-blind, double-dummy, parallel-group, phase III, noninferiority clinical trial.
"Chiral switching" from an existing racemate to a pure enantiomeric compound is a popular theme in drug development, especially when the enantiomer is found to have better efficacy and safety profiles. Amlodipine is a racemic mixture, composed of the S(-)-enantiomer, which is the pharmacologically active isomer, and the R(+)-enantiomer, which is 1000-fold less active. S(-)-amlodipine nicotinate, a chirally switched form of amlodipine nicotinate, has been developed and found to be bioequivalent to amlodipine besylate in Phase I clinical trials in Korea. ⋯ The reduction of SiDBP after 8 weeks of treatment with S(-)-amlodipine nicotinate was noninferior compared with that of racemic amlodipine besylate in these adult Korean patients with mild to moderate hypertension. The SiDBP response rate and the reduction of SiSBP after 8 weeks of treatment with S(-)-amlodipine nicotinate were not significantly different from those with racemic amlodipine besylate. Both treatments were generally well tolerated.
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Clinical therapeutics · May 2008
Randomized Controlled Trial Multicenter Study Comparative StudyEfficacy and tolerability of IV doripenem versus meropenem in adults with complicated intra-abdominal infection: a phase III, prospective, multicenter, randomized, double-blind, noninferiority study.
Complicated intra-abdominal infections (cIAIs) require surgical intervention and empiric antibacterial therapy. Doripenem, a broad-spectrum carbapenem, provides coverage of key gram-negative and -positive aerobes and anaerobes encountered in cIAI. ⋯ The present study found that doripenem (500 mg q8h) was effective in the treatment of cIAI, was therapeutically noninferior to meropenem (1 g q8h), with a safety profile not significantly different from that of meropenem in this selected population of patients with cIAI.
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Clinical therapeutics · May 2008
ReviewA review of the efficacy of smoking-cessation pharmacotherapies in nonwhite populations.
Cigarette smoking continues to be the leading cause of preventable morbidity and mortality in the United States. Research suggests that behavioral support strategies and pharmacotherapy can improve abstinence rates. However, both approaches, especially pharmacotherapy, have been understudied in nonwhite US populations. ⋯ Data from the studies in this review support the use of smoking-cessation pharmacotherapy (nicotine patch and bupropion SR) in nonwhite patients. Black patients, who smoked within 30 minutes of awakening, smoked mentholated cigarettes, and had high salivary cotinine levels may have difficulty quitting regardless of the number of cigarettes smoked per day; therefore, determining the type of cigarettes smoked (mentholated vs nonmentholated) and salivary cotinine levels may be helpful in assessing the severity of smoking addiction and guide pharmacotherapy (eg, starting at higher doses of nicotine-replacement therapy in a light smoker). Other than smoking-cessation behavioral studies, there is a lack of congruent smoking-cessation pharmacotherapy studies in American Indian/Alaska Native, Hispanic, and other ethnic populations.
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Clinical therapeutics · May 2008
ReviewRole of corticosteroids in the management of acute respiratory distress syndrome.
Evidence exploring the use of corticosteroids for acute respiratory distress syndrome (ARDS) has targeted various stages of disease progression, from preventing ARDS in high-risk patients to halting disease evolution once ARDS has developed. ⋯ Data from clinical trials did not support the use of short-course, high-dose corticosteroids for preventing ARDS or for the treatment of early ARDS. Longer-course corticosteroids have not conclusively been associated with improved survival in the treatment of late-phase ARDS but have provided some benefits in other markers of disease severity in this setting and in early phase ARDS. Published trials support the administration of low- to moderate-dose corticosteroids in the treatment of early (<7 days) and late-phase (days 7\2-14) ARDS, but this evidence is controversial.
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Clinical therapeutics · May 2008
Meta AnalysisEfficacy and tolerability of alosetron for the treatment of irritable bowel syndrome in women and men: a meta-analysis of eight randomized, placebo-controlled, 12-week trials.
Stimulated 5-hydroxytryptamine-3 (5-HT(3)) receptors promote intestinal motility, secretion, and sensation, effects that are related to the known pathophysiology of irritable bowel syndrome (IBS). A previous meta-analysis of 6 randomized controlled trials of the 5-HT(3)-receptor antagonist alosetron found that this agent was associated with global improvement in symptoms, pain, and discomfort in patients with IBS. ⋯ Alosetron was effective in these men and women with IBS. constipation was the most frequently reported adverse event associated with alosetron therapy. Ischemic colitis and serious complications of constipation were reported in a small number of patients treated with alosetron.