Expert opinion on investigational drugs
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Expert Opin Investig Drugs · Oct 2008
ReviewJanumet: a combination product suitable for use in patients with Type 2 diabetes.
Inhibition of the enzyme dipeptidyl peptidase-4 represents the latest pharmacologic intervention to become available to assist patients with Type 2 diabetes to achieve glycemic control. A combination tablet of sitagliptin (Januvia) and metformin HCl (Glucophage) is now available from Merck (Janumet). ⋯ Sitagliptin has been shown to be safe and effective at 100 mg daily doses. When given in combination with metformin the effect on glycemic control is thought to be complementary and possibly additive.
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Expert Opin Investig Drugs · Oct 2008
ReviewTherapeutic potential of inhaled p38 mitogen-activated protein kinase inhibitors for inflammatory pulmonary diseases.
Over the past two decades, p38 MAPK (mitogen-activated protein kinase) has been the subject of intense multidisciplinary research. p38 MAPK inhibitors have been shown to be efficacious in several disease models, including rheumatoid arthritis, psoriasis, Crohn's disease, and stroke. Recent studies support a role for p38 MAPK in the development, maintenance, and/or exacerbation of a number of pulmonary diseases, such as asthma, cystic fibrosis, idiopathic pulmonary fibrosis, and chronic obstructive pulmonary disease (COPD). ⋯ We present proof-of-principle confirming the therapeutic potential of inhaled p38 inhibitors for asthma and other inflammatory pulmonary diseases.
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Expert Opin Investig Drugs · Sep 2008
Methylnaltrexone, a new peripherally acting mu-opioid receptor antagonist being evaluated for the treatment of postoperative ileus.
Postoperative ileus (POI), a transient impairment of bowel function, is considered an inevitable response after open abdominal surgery. It leads to significant patient morbidity and increased hospital costs and length of stay. The pathophysiology is multifactorial, involving neurogenic, hormonal, inflammatory and pharmacologic mediators. ⋯ Two Phase III trials have been completed, and one is underway at present. Preliminary results from the two completed trials indicate that methylnaltrexone was not better than placebo for the primary or secondary outcomes. Further analyses of these data, clinical trial designs and the various dosage forms are necessary to determine the potential role of methylnaltrexone in the treatment of POI.
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Expert Opin Investig Drugs · Aug 2008
ReviewNovel biologic mechanisms of levosimendan and its effect on the failing heart.
Calcium sensitizers belong to a new class of cardiac enhancers that stimulate cardiac contractility without causing intracellular calcium overload or increasing myocardial oxygen demand. Levosimendan, the most well-studied calcium sensitizer in the real clinical practice, produces greater hemodynamic and symptomatic improvement in patients with acute heart failure than traditional inotropes. ⋯ Pleiotropic effects of levosimendan appear to have important clinical and prognostic implications in acute heart failure syndromes and ischemic heart disease.
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Induced hypothermia is a promising neuroprotective treatment for acute ischemic stroke. Data from both global and focal ischemia animal models have been encouraging. However, only a few small clinical studies have investigated its use in humans. ⋯ Induced hypothermia is effective as a neuroprotectant in animal models of acute ischemic stroke. Its multimodal mechanism of action makes it a very attractive method of neuroprotection. Although human studies suggest it is safe and feasible, larger randomized controlled trials are necessary to address clinical efficacy and to refine the methods and parameters of induced hypothermia protocols.