The comparative pharmacokinetics of physical manipulation by crushing of Xtampza® ER compared with OxyContin®.

AIM: To further characterize the pharmacokinetics of Xtampza® ER. SUBJECTS & METHODS: This was an open-label, randomized, active-controlled, five-treatment, five-period, naltrexone-blocked, cross-over study. Healthy subjects received five equivalent oxycodone doses: Xtampza ER (intact or crushed), OxyContin® (intact or crushed) or immediate-release (IR) oxycodone (crushed). Blood samples were collected to assess oxycodone concentrations. RESULTS: Crushed and intact Xtampza ER resulted in lower peak plasma concentrations compared with crushed oxycodone IR; crushed and intact Xtampza ER were bioequivalent. Crushed OxyContin exhibited a rapid increase in plasma oxycodone and was bioequivalent to crushed oxycodone IR. CONCLUSION: This second pharmacokinetic study demonstrated that Xtampza ER maintains its ER properties after crushing, unlike OxyContin, which failed to retain its ER properties after crushing. ANZCTR registration number: ACTRN12614000613606.

An abuse-deterrent, microsphere-in-capsule formulation of extended-release oxycodone: alternative modes of administration to facilitate pain management in patients with dysphagia.

BACKGROUND: Patients with chronic pain may experience difficulty swallowing, in part due to worsening disease, comorbid conditions, iatrogenic etiology, or age. Patients or caregivers may manipulate extended-release (ER) opioid formulations to facilitate oral dosing due to a lack of therapeutic options that allow for sprinkle or enteral feeding tube administration. If crushed or broken, current oral ER opioids can be associated with adverse sequelae, including risk of potentially fatal overdose. OBJECTIVE: To review the safety, in vitro dissolution data, and in vivo pharmacokinetic data that support alternative modes of administration of oxycodone DETERx (Xtampza ER) via sprinkling onto soft foods for oral ingestion or via enteral feeding tubes. METHODS: A review of oxycodone DETERx data from in vitro and in vivo studies was conducted to demonstrate support for alternative routes and modes of administration. RESULTS: There was no difference in the dissolution profile when administered with various soft foods or when mixed with various liquid vehicles and administered via nasogastric (NG) or gastrostomy (G) tubes, based on in vitro studies. When sprinkled onto applesauce and administered orally, the microspheres were bioequivalent to the intact oxycodone capsules. When crushed or chewed, the formulation maintained its pharmacokinetic profile; no bolus dose of opioid was released. The sprinkle-dose study was limited by the single-dose study design, as well as the small sample size. CONCLUSIONS: Oxycodone DETERx is the first ER oxycodone formulation that can be administered either intact, sprinkled onto soft foods, or via NG/G tubes, thereby providing options for treating pain in patients who have difficulty swallowing.

Ascorbate treatment attenuates the Huntington behavioral phenotype in mice.

The R6/2 mouse line expresses exon 1 of the human gene for Huntington disease (HD) and shows behavioral symptoms as early as 6 weeks of age. In the striatum, a forebrain target of HD, these animals show a behavior-related deficit in extracellular ascorbate, the deprotonated form of vitamin C. We report here that this deficit may contribute to the HD behavioral phenotype. Regular injections of ascorbate (300 mg/kg/day, 4 days/week) beginning at symptom onset restored the behavior-related release of ascorbate in striatum and also improved behavioral responding. Compared to vehicle, ascorbate treatment significantly attenuated the neurological motor signs of HD without altering overall motor activity. Ascorbate regulation of striatal function appears key for understanding HD.