A Phase I study of the pharmacokinetics, safety and tolerability of a novel tocopheryl phosphate mixture/oxymorphone transdermal patch system.

Aim: Characterize the pharmacokinetic profile and tolerability of two tocopheryl phosphate mixture/oxymorphone patch formulations in healthy subjects, and the active metabolite (6-OH-oxymorphone).

Materials & Methods: Fifteen participants received a single application of oxymorphone patches +/- capsaicin for 72 h and were crossed-over for another 72 h.

Results: Plasma oxymorphone was detected approximately 7 h and 6-OH-oxymorphone after approximately 18-19 h postapplication of both formulations, respectively.

Pharmacokinetics, safety and tolerability of a novel tocopheryl phosphate mixture/oxycodone transdermal patch system: a Phase I study.

Aim: To characterize the pharmacokinetic profile and evaluate the safety and tolerability of a transdermal oxycodone patch containing tocopheryl phosphate mixture (TPM).

Patients & Methods: Eleven healthy subjects received a single application of three TPM/oxycodone patches applied to the torso for 72 h.

Results: Oxycodone was detected 8.

Motor skill learning induces changes in white matter microstructure and myelination.

Learning a novel motor skill is associated with well characterized structural and functional plasticity in the rodent motor cortex. Furthermore, neuroimaging studies of visuomotor learning in humans have suggested that structural plasticity can occur in white matter (WM), but the biological basis for such changes is unclear. We assessed the influence of motor skill learning on WM structure within sensorimotor cortex using both diffusion MRI fractional anisotropy (FA) and quantitative immunohistochemistry.

A genetically-encoded chloride and pH sensor for dissociating ion dynamics in the nervous system.

Within the nervous system, intracellular Cl(-) and pH regulate fundamental processes including cell proliferation, metabolism, synaptic transmission, and network excitability. Cl(-) and pH are often co-regulated, and network activity results in the movement of both Cl(-) and H(+). Tools to accurately measure these ions are crucial for understanding their role under physiological and pathological conditions.

MorphiDex (morphine sulfate/dextromethorphan hydrobromide combination) in the treatment of chronic pain: three multicenter, randomized, double-blind, controlled clinical trials fail to demonstrate enhanced opioid analgesia or reduction in tolerance.

While many pre-clinical and clinical studies have suggested that the addition of N-methyl-D-aspartate (NMDA) receptor antagonists, such as dextromethorphan (DM), to opioid analgesics, such as morphine (MS), may enhance the analgesic effects and prevent the tolerance that may result from chronic opioid administration, others have not. The potential for reduced doses, enhanced opioid analgesia, and decreased analgesic tolerance associated with the MS/DM combination were evaluated in a series of three large, randomized, double-blind, parallel group, phase 3, multicenter trials each of 3 months duration in patients with chronic, non-malignant, non-neuropathic pain. To evaluate these unique endpoints, novel study designs were employed.