Aim Dual enkephalinase inhibitors (DENKIs) are involved in the regulation of nociception via opioid receptors. The novel compound STR-324 belongs to the DENKI pharmacological class. This first-in... Show moreAim Dual enkephalinase inhibitors (DENKIs) are involved in the regulation of nociception via opioid receptors. The novel compound STR-324 belongs to the DENKI pharmacological class. This first-in-human study evaluated the safety, tolerability, pharmacokinetics and pharmacodynamics of STR-324 in healthy male participants. Methods This was a randomised, double-blind, placebo-controlled ascending dosing study in two parts: in part 1, 30 participants received 0.004-11.475 mg h(-1) of STR-324 or placebo (ratio 4:1) by 4 h intravenous infusion in a two-group, partial crossover design with four treatment periods separated by 1 month wash-out, and in part 2, 48 participants divided into three groups received either the active drug (1.25-11.25 mg h(-1)) or placebo (ratio 3:1) by 48 h intravenous infusion. Safety and tolerability parameters, pharmacokinetics and pharmacodynamic effects on neurocognitive and neurophysiological tasks and on a nociceptive test battery were evaluated. Results No clinically relevant changes in safety parameters were observed. All treatment-emergent adverse events were mild and transient. The pharmacokinetics of STR-324 could not be determined due to most concentrations being below quantifiable limits. STR-324 metabolite concentrations were measurable, showing dose proportionality of C-max and AUC(inf) with an estimated t(1/2) of 0.2-0.5 h. Significant changes in pharmacodynamic parameters were observed, but these were not consistent or dose-dependent. Conclusion STR-324 displayed favourable safety and tolerability profiles at all doses up to 11.475 mg h(-1). Although pharmacokinetic characterisation of STR-324 was limited, dose proportionality could be assumed based on major metabolite data assayed as proxy. No clear effects on nociceptive thresholds or other pharmacodynamic measures were observed. Trial registry: EudraCT (2014-002402-21) and toetsingonline.nl (63085). Show less
The recognition and treatment of pain in nursing home residents presents challenges best addressed by a multidisciplinary approach. This approach is also recommended in the applicable Dutch... Show moreThe recognition and treatment of pain in nursing home residents presents challenges best addressed by a multidisciplinary approach. This approach is also recommended in the applicable Dutch guideline; however, translating guidelines into practical strategies is often difficult in nursing homes. Nevertheless, a better understanding of guideline implementation is key to improving the quality of care. Here we describe and qualitatively evaluate the implementation process of the multidisciplinary guideline 'Recognition and treatment of chronic pain in vulnerable elderly' in a Dutch nursing home. The researchers used interviews and document analyses to study the nursing home's implementation of the guideline. The project team of the nursing home first filled out an implementation matrix to formulate goals based on preferred knowledge, attitudes, and behaviors for the defined target groups. Together with experts and organizations, pharmacotherapy audit meetings were organized, an expert pain team was appointed, a policy document and policy flowchart were prepared, and 'anchor personnel' were assigned to disseminate knowledge amongst professionals. Implementation was partially successful and resulted in a functioning pain team, a pain policy, the selection of preferred measurement instruments, and pain becoming a fixed topic during multidisciplinary meetings. Nevertheless, relatively few professionals were aware of the implementation process. Show less
