Expert opinion on investigational drugs
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Expert Opin Investig Drugs · Aug 2001
ReviewCaspofungin: pharmacology, safety and therapeutic potential in superficial and invasive fungal infections.
Invasive fungal infections are important causes of morbidity and mortality in hospitalised patients. Current therapy with amphotericin B and antifungal triazoles has overlapping targets and is limited by toxicity and resistance. The echinocandin lipopeptide caspofungin is the first of a new class of antifungal compounds that inhibit the synthesis of 1,3-beta-D-glucan. ⋯ Based on its documented antifungal efficacy and an excellent safety profile, caspofungin has been approved recently by the US Food and Drug Administration for the treatment of invasive aspergillosis in patients who are refractory to or intolerant of other therapies (i.e., amphotericin B, lipid formulations of amphotericin B, and/or itraconazole). Phase III clinical trials in patients with candidaemia and in persistently febrile neutropenic patients requiring empirical antifungal therapy are ongoing. This paper reviews the preclinical and clinical pharmacology of caspofungin and its potential role for treatment of invasive and superficial fungal infections in patients.
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Expert Opin Investig Drugs · Aug 2001
ReviewBotulinum toxin therapy for pain and inflammatory disorders: mechanisms and therapeutic effects.
Botulinum toxin (BTX) injections are a well-recognised therapeutic modality for the treatment of regional involuntary muscle disorders and recently BTX has been used for treatment of pain and inflammatory disorders. The primary purpose of this review is to discuss the mechanism of action of therapeutic BTX in light of both the traditional understanding of BTX pharmacological effects as well as new observations. The review will deal with clinical observations and relevant animal experimentation. ⋯ The complex proteins may also have unrecognised clinical significance such as slowing diffusion in tissues or imparting stability. The mechanisms of BTX formulations acting on SNARE proteins are briefly reviewed providing a basis for BTX clinical applications. The potential for design of improved botulinum toxins and formulations is addressed.
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Expert Opin Investig Drugs · Aug 2001
ReviewExperimental and emerging therapies for sepsis and septic shock.
The underlying principles of sepsis therapy have remained unchanged for decades. These include: prompt institution of antimicrobial agents aimed at the inciting pathogen, source control directed at removal of the infection nidus whenever possible, and support of organ dysfunction. Despite advances in antibiotics, surgical techniques and organ support technology, the morbidity and mortality from sepsis-related diseases have remained substantially unchanged (30 - 50%). ⋯ In this first of a three part series, we go through some of the background and current strategies in sepsis therapy. In this review, we include the two novel therapies that have shown clear survival benefit in large, randomised, placebo-controlled, multi-centre trials, low-dose steroids and recombinant activated protein C. Also included in this review are studies on antithrombin III, platelet-activating factor antagonists, complement modulators, nitric oxide synthase inhibitors and caspase inhibitors (apoptosis inhibitors).