Nalmefene is a high‐affinity, long‐duration opioid antagonist that was approved in 1995 as an injection for the treatment of opiate overdose, but subsequently withdrawn (2008) for reasons other than safety or effectiveness. The dramatic rise in opioid overdose deaths over the past 7‐8 years catalyzed the development of an intranasal (IN) formulation of nalmefene for the emergency treatment of opioid overdose. The studies described here compare the pharmacokinetic properties and safety profiles of an IN formulation containing nalmefene (2.7 mg in 0.1 mL) to an approved 1 mg intramuscular (IM) dose. IN nalmefene produced maximum plasma concentrations that were significantly higher than observed following the IM dose (12.2 and 1.77 ng/mL, respectively). The time to reach maximum plasma concentrations was also faster following IN administration (0.25 and 0.33 hours, respectively) with significant differences in plasma concentrations manifested as early as 2.5 minutes after administration (NCT04759768). The plasma half‐life of nalmefene was similar following IM and IN administration (10.6‐11.4 hours). Furthermore, dose‐normalized nalmefene exposure was similar for both 1 spray in each nostril and 2 sprays in the same nostril compared to a single spray in each nostril (NCT05219669). There were no sex differences in the pharmacokinetic properties of either IN or IM nalmefene. In an era when almost 90% of opioid overdose deaths have been linked to high‐potency synthetic opioids, the ability to rapidly deliver high concentrations of nalmefene could represent an important tool for reducing both morbidity and mortality.
The proposed mechanism of action for pentoxifylline's beneficial effect in peripheral vascular disease is an improvement in red blood cell deformability. Likewise, single doses of pentoxifylline in healthy volunteers have been shown to improve whole blood filterability, which was suggested to occur as a result of augmented red blood cell deformability. To further assess this, the authors studied the effects of short-term pentoxifylline administration (400 mg three times daily for 7 days) on red blood cell deformability in ten healthy, methylxanthine-free, nonsmoking volunteers. Blood samples were obtained at baseline and after 1 week of therapy (steady-state). Samples were analyzed for red blood cell deformability by ektacytometry, which showed no significant change in deformability in any subject. Despite the improvement in whole blood filterability associated with both single-dose and short-term administration of pentoxifylline, the current study demonstrates no effect on red blood cell deformability after short-term administration in healthy volunteers.
A 1-month elective course in clinical pharmacology in primary care has been developed and is offered six times a year for fourth-year medical students. The major course objective is to teach the student to apply the principles of rational therapeutics in the routine practice of primary care. The faculty includes clinical pharmacists and primary care physicians from the Department of Family Medicine. Two students each month rotate through a combined didactic and experiential curriculum oriented toward the rational selection and monitoring of drugs in inpatient and outpatient settings. Students interact daily with faculty members and have ample opportunity to evaluate drug therapy regimens and assist in designing new therapeutic strategies. Students are evaluated on their performance in conferences, written consultations, and oral case challenges. Evaluations by students indicate that this elective is a valuable educational experience.
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