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

  title={Pharmacokinetics of NXY-059, a nitrone-based free radical trapping agent, in healthy young and elderly subjects.},
  author={Charlotte Edenius and Stig Strid and Olof Borg{\aa} and Anna Breitholtz-Emanuelsson and Kerstin Lanbeck Vall{\'e}n and Bo Fransson},
  journal={Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association},
  volume={11 1},
  • C. Edenius, S. Strid, +3 authors B. Fransson
  • Published 2002
  • Medicine
  • Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association
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 5.25 micromol/kg/h (0.06 to 2.0 mg/kg/h). In the second study, elderly male and female… Expand
Pharmacokinetics in renally impaired subjects of NXY-059, a nitrone-based, free-radical trapping agent developed for the treatment of acute stroke
Non-renal elimination of N XY-059 appeared to be insignificant even in subjects with low renal capacity, and patients with renal impairment should have their dose of NXY-059 adjusted for renal function, conveniently assessed from serum creatinine. Expand
Safety, tolerability and pharmacokinetics of escalating doses of NXY-059 in healthy young and elderly subjects*
NXY-059 was well tolerated at all plasma concentrations tested in both the young and elderly subjects, and no safety concerns were raised. Expand
Pharmacokinetics of 8-hour intravenous infusion of NXY-059: a phase I, randomized, double-blind (within dose panels), placebo-controlled study in healthy Chinese volunteers.
The results from the present study suggest that the PK properties of NXY-059 were similar in the Chinese and historical white healthy volunteer populations. Expand
Effect of NXY-059, a novel neuroprotectant, on the pharmacokinetics of a single dose of digoxin in healthy subjects
NXY‑059 had no clinically significant effect on the PK of digoxin, and the most common adverse event was headache with similar frequencies in the two treatments. Expand
NXY‐059 Does Not Significantly Interact With Furosemide in Healthy Volunteers
This double‐blind, randomized, crossover, placebo‐controlled study investigated whether an infusion of NXY‐059 affects the diuretic and saluretic effects of a 30‐mg intravenous bolus dose of furosemide administered after 6 hours' infusion. Expand
A Study of Organic Acid Transporter‐Mediated Pharmacokinetic Interaction Between NXY‐059 and Cefuroxime
The primary objectives of this study were to explore the effect of NXY-059 on the renal clearance (CLR) of the model drug cefuroxime and to estimate the degree of interaction to be expected with N XY-059 when coadministered with other drugs mainly eliminated by the kidney, with some contribution from active transportation by OAT. Expand
A phase 1, placebo-controlled, randomised, double-blind (within dose panels) study evaluating the safety, tolerability and pharmacokinetics of intravenous NXY-059 in Japanese subjects
The safety, tolerability and pharmacokinetics of NXY‑059 in healthy Japanese male subjects and Caucasians are similar, and there was no evidence of any vasoirritative effects or changes in renal function. Expand
Active Renal Secretion of NXY‐059, a Novel Neuroprotectant, Is Mediated via an Organic Acid Transporter
The study concluded that the contribution of nonrenal clearance to the overall clearance of N XY-059 was negligible and the possibility also exists that NXY-059 could be secreted by an active transporter for organic bases. Expand
Population Pharmacokinetic Modelling and Estimation of Dosing Strategy for NXY-059, a Nitrone Being Developed for Stroke
The results illustrate how an individualised dosing strategy, given a pharmacokinetics target, for NXY-059 was successfully optimised through estimation using the increasing pharmacokinetic and pharmacodynamic knowledge during a clinical drug development programme. Expand
NXY-059: Review of Neuroprotective Potential for Acute Stroke
Initial safety and efficacy data have not revealed any serious adverse events requiring special monitoring and/or precautions, with the exception of drug accumulation in patients with renal insufficiency. Expand


Tolerability and Pharmacokinetics of the Nitrone NXY-059 in Patients With Acute Stroke
NXY-059 was well tolerated in patients with an acute stroke, and the testing of higher doses in future trials may be justified. Expand
Neuroprotective Effects of a Novel Nitrone, NXY-059, after Transient Focal Cerebral Ischemia in the Rat
Studies of the transfer constant of [14C]NXY-059 showed that, in contrast to PBN, this more soluble nitrone penetrates the blood-brain barrier less extensively, suggesting that the delayed events leading to infarction may be influenced by reactions occurring at the blood–endothelial interface. Expand
NXY-059, a Free Radical–Trapping Agent, Substantially Lessens the Functional Disability Resulting From Cerebral Ischemia in a Primate Species
This novel drug has a substantial protective effect, lessening the disability caused by an experimentally induced stroke in a primate species, and these findings provide considerable encouragement for the clinical development of NXY-059. Expand
Chronopharmacokinetics. Current status.
Drug chronopharmacokinetic knowledge may be clinically relevant as it may have implications for drug prescription by modulating the distribution of the total daily dose along the 24-hour scale and should be considered in specific cases related to patients, illness or the drug itself. Expand
Discrepancy between circadian rhythms of inulin and creatinine clearance.
Tubular creatinine secretion has a circadian rhythm with a phase opposite to the rhythm of GFR, thus blunting or causing absence of a circadian Rhythm Counteracting, the normal rhythmicity of glomerular filtration of Creatinine. Expand
Evaluation of Creatinine Clearance Estimation in an Elderly Male Population
The results support using methods to estimate creatinine clearance only as a rough bedside prediction of renal function in elderly males through a prospective study evaluating the accuracy of 16 methods. Expand
Circadian rhythm of glomerular filtration rate in normal individuals
1. In a group of 11 normal individuals we measured glomerular filtration rate (GFR) by inulin clearances and effective renal plasma flow (ERPF) by p-aminohippurate clearances during a period of 24 hExpand
Trials of thrombolysis in acute ischemic stroke: does the choice of primary outcome measure really matter?
BACKGROUND AND PURPOSE Controversy regarding the risks and benefits of thrombolysis has not been helped by the perception that some trials were "positive" and others "negative" on their primaryExpand
Prediction of Creatinine Clearance from Serum Creatinine
A formula has been developed to predict creatinine clearance (Ccr) from serum creatinine (Scr) in adult males: Ccr = (140 – age) (wt kg)/72 × Scr(mg/100ml) (15% less i
Epidemiology of stroke