Pharmacokinetics of NXY-059, a nitrone-based free radical trapping agent, in healthy young and elderly subjects.

The tolerability, safety, and pharmacokinetics of NXY-059, a nitrone-based free radical trapping agent under development for the treatment of acute ischemic stroke, were investigated in 2 double-blind, placebo-controlled dose-escalation studies in healthy subjects. In the first study in 6 panels of young male subjects (n = 48, 22-45 years), constant rate infusions lasted 8 hours and ranged from 0.16 to 5.

Safety, tolerability and pharmacokinetics of escalating doses of NXY-059 in healthy young and elderly subjects.

Objective: NXY-059 is a novel, free-radical trapping, neuroprotectant that reduces infarct size and preserves brain function in animal models of acute ischaemic stroke. This study evaluated the safety, tolerability and pharmacokinetics of NXY-059 in the unbound steady-state plasma concentration (Cu(ss)) exposure range of 50-300 micromol/L in healthy young and elderly subjects.

Research Design And Methods: The primary objective of this two-centre, randomised, double-blind, placebo-controlled, dose-escalating study was to investigate the safety and tolerability, including renal function parameters and vasoirritative effects, of 8-h and 72-h intravenous infusions of NXY-059 in healthy young (20-45 years) and elderly (55-75 years) male and female subjects.

Brain penetration of the novel free radical trapping neuroprotectant NXY-059 in rats subjected to permanent focal ischemia.

The penetration of the free radical trapping neuroprotectant NXY-059 into the brain has been examined in rats subjected to permanent middle cerebral artery occlusion (pMCAO). NXY-059 (125 mg/kg bolus followed by 125 mg/kg/h) was infused for 4 h 45 min starting 15 min after right pMCAO or sham operation. At 5 h, there was a similar plasma total NXY-059 concentration (micromol/L) in both groups [sham: 623 +/- 44 (6); pMCAO: 605 +/- 43 (5)] and a similar drug concentration (nmol/g) in the right cortex [sham: 6.