Fentanyl buccal tablet: faster rescue analgesia for breakthrough pain?

Breakthrough pain (BTP) is an unmet clinical need that is still poorly diagnosed, evaluated and inadequately treated. The prevalence of BTP has been estimated to affect at least 64% of cancer patients. Two pain-relief strategies were proposed: preventive and active ('rescue'). Oral short-acting opioid seems to be the most popular approach for BTP treatment, however, it is likely to be inadequate for a substantial proportion of patients as a result of the slow-onset of most available opioid preparations. Fentanyl buccal tablet (FBT) is a novel delivery system for fentanyl citrate. FBT utilizes OraVescent technology to improve bioavailability and speed of drug delivery. Recent studies have demonstrated superior pharmacokinetic profiles when compared with other available transmucosal opioids (OTFC), however, pharmacodynamic data are still somewhat limited.     

Gut Mucosal Injury Is Attenuated by Recombinant Bactericidal/Permeability-Increasing Protein in Hind Limb Ischemia-Reperfusion Injury

Lower limb ischemia-reperfusion injury (IRI) is associated with increased gut permeability to endotoxin, which not only directly damages enterocytes but also stimulates a systemic inflammatory response syndrome (SIRS), compounding gut injury. Recombinant bactericidal/permeability-increasing protein (rBPI21) is a novel anti-endotoxin therapy with proven benefit in sepsis. Its potential role in modulating remote gut injury in hind limb IRI was studied. Male Wistar rats were chosen for a prospective randomized control trial (n = 10 per group). The control group and two groups undergoing 3 hr bilateral hind limb ischemia with 2 hr reperfusion (I/R) were randomized to receive intravenously either control protein thaumatin at 2 mg/kg or rBPI21 at 2 mg/kg, respectively. Quantitative morphometric assessment of the small bowel was used as a measure of gut injury and, using an ex vivo everted gut sac model, translocation of 14C-labeled polyethylene glycol (PEG) was used as a measure of gut permeability. Our results indicate that hind limb IRI is associated with remote gut mucosal injury and increased permeability to macromolecules. rBPI21 anti-endotoxin therapy modulates remote gut injury associated with lower limb IRI in this model.