British journal of clinical pharmacology
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Br J Clin Pharmacol · Aug 2011
Randomized Controlled TrialSB-656933, a novel CXCR2 selective antagonist, inhibits ex vivo neutrophil activation and ozone-induced airway inflammation in humans.
Receptor antagonists that block the binding of chemokines such as CXCL8 (IL-8) are effective in animals models of neutrophil-mediated inflammation. It has been hypothesized that selective inhibition of neutrophil trafficking and activation may be a useful adjunct for the treatment of inflammatory airway diseases such as chronic obstructive pulmonary disease or cystic fibrosis. A CXCR1/2 receptor antagonist has shown activity in an ozone challenge model in humans. ⋯ SB-656933 is a CXCR2 antagonist that demonstrates dose-dependent effects on neutrophil activation and recruitment within a well-tolerated dose range. These data suggest that SB-656933 may be an effective agent in neutrophil-predominant diseases.
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Br J Clin Pharmacol · Aug 2011
Randomized Controlled TrialPharmacokinetics, pharmacodynamics and safety of a human anti-IL-6 monoclonal antibody (sirukumab) in healthy subjects in a first-in-human study.
Interleukin (IL)-6 is a cytokine known for pleiotropic and pro-inflammatory functions. IL-6 is involved in various disease processes including lupus erythematosus, rheumatoid arthritis, insulin resistance and malignancy. Anti-IL-6 receptor therapy has recently been demonstrated to be effective in the treatment of patients with rheumatoid arthritis. ⋯ Sirukumab had a well-tolerated safety profile, desirable PK characteristics and a low incidence of immunogenicity following an i.v. infusion of 0.3 to 10 mg kg(-1) in healthy subjects.
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Br J Clin Pharmacol · Aug 2011
Deaths of opiate/opioid misusers involving dihydrocodeine, UK, 1997-2007.
Dihydrocodeine (DHC) is an opioid analgesic sometimes prescribed as an alternative to other medications (e.g. methadone and buprenorphine) for opioid misuse. Its effectiveness is, however, still controversial. DHC prescription rates seem to be related to levels of DHC fatalities, possibly in relation to levels of disregard of the availability of supervised or interval dispensing of opioids, but no large-scale analysis of DHC fatalities has been carried out. We analysed here involvement of DHC in fatalities that occurred between 1997 and 2007 among individuals with a history of opiate/opioid misuse reported to the National Programme on Substance Abuse Deaths (np-SAD). ⋯ Opiate/opioid misusers should be educated about risks associated with polydrug intake. More in particular, co-administration of DHC with heroin, methadone and benzodiazepines may increase the risk of accidental fatal overdose. Prescribers should carefully consider pharmacological intervention alternative to DHC (e.g. methadone, buprenorphine) when managing and treating opiate addiction. More resources are required to do prospective research in this area.