Expert opinion on investigational drugs
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Expert Opin Investig Drugs · Nov 2011
ReviewThe evolving experience with therapeutic TNF inhibition in sepsis: considering the potential influence of risk of death.
Septic shock is highly lethal and its incidence is increasing. Although TNF-α plays a key role in sepsis pathogenesis, past efforts to therapeutically inhibit it had limited success. However, there is continued interest in such therapies and there are now ongoing Phase II sepsis trials testing the effects of AZD9773, a TNF-directed polyclonal antibody fragment preparation. Experience with anti-inflammatory agents suggested that their efficacy may relate to sepsis-associated risk of death. ⋯ Discusses variables that may need to be accounted for to maximize the success of clinical trials in sepsis testing agents that modulate host inflammation.
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Expert Opin Investig Drugs · Oct 2011
The safety and tolerability evaluation of DepoFoam bupivacaine (bupivacaine extended-release liposome injection) administered by incision wound infiltration in rabbits and dogs.
DepoFoam bupivacaine (DB) is in development for prolonged postoperative analgesia. Studies were conducted to evaluate the potential local and systemic toxicity and any effect on wound healing after wound infiltration. ⋯ The data reported here are the first demonstration of the safety of DB in toxicology species.
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Expert Opin Investig Drugs · Sep 2011
ReviewTargeting voltage-gated calcium channels for the treatment of neuropathic pain: a review of drug development.
Pain is a major burden for affected individuals and society, and controlling neuropathic pain is especially challenging. The number of drugs available is limited and treatments are often marginally effective and burdened by side effects. Voltage-gated calcium channels (VGCC) play a major role in the development and maintenance of neuropathic pain and are thus prime targets for its treatment. ⋯ There is real hope that new drugs targeting calcium channels will soon be available. This hope is based on advancing technologies for peptide synthesis, more efficient drug screening and orally available, use-dependent compounds. Some form of direct VGCC blockade or modulation will always have a place in the treatment of neuropathic pain, but given the complexity and neuroplasticity of pain transmission, polypharmacy will likely be required for many chronic pain sufferers for the foreseeable future.
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Expert Opin Investig Drugs · Aug 2011
ReviewNovel opioid antagonists for opioid-induced bowel dysfunction.
Adverse effects frequently limit the therapeutic benefits of opioid analgesics. Gastrointestinal adverse effects are common, burdensome, and can compromise the quality of life. It is estimated that up to 81% of patients still report constipation despite regular use of laxatives. Thus, the development of opioid antagonists that selectively target receptors in the gut without affecting central analgesia has provided new perspectives on the treatment of opioid-induced gastrointestinal adverse effects. ⋯ Two strategies effectively relieve OBD without interfering with centrally mediated analgesia: the administration of opioid antagonists with limited systemic absorption and peripherally acting mu-opioid receptor antagonists (PAMORA) that selectively target mu-receptors in the gastrointestinal tract. Methylnaltrexone and alvimopan are two recently marketed PAMORA and provide a new mechanism-based approach for the treatment of opioid-induced gastrointestinal dysfunction. However, its use in clinical practice is limited by various reasons such as its relatively low response rates and higher costs. Nevertheless, at least four new oral PAMORA (NKTR-118, TD-1211, ADL-7445, and ADL-5945) are under clinical development, further expanding the possibilities for a new paradigm for OBD management.