Effect of NXY-059, a novel neuroprotectant, on the pharmacokinetics of a single dose of digoxin in healthy subjects.
OBJECTIVE
NXY-059 is a novel free-radical trapping neuroprotectant. Digoxin treatment is common in acute ischaemic stroke, the intended patient population for NXY-059. Since both digoxin and NXY-059 are eliminated primarily renally, with a substantial contribution by active renal secretion, and because digoxin has a narrow therapeutic window, this open, randomised, crossover, two-period study investigated whether NXY-059 affects the pharmacokinetics (PK) of digoxin.


METHODS
Twenty-two healthy subjects received 0.5 mg oral digoxin 2 h after the start of 60-h intravenous infusions of NXY-059 and placebo separated by a 14-day washout. Blood and urine were collected for 60 h. Digoxin concentrations were measured by a novel liquid chromatography-mass spectrometry assay.


METHODS
The ratio of the geometric mean (90% confidence interval) between NXY-059 and placebo for the digoxin area under the concentration-versus-time curve was 0.91 (0.83-0.99) and was within the predefined range for no interaction (0.80-1.25). No safety concerns were raised in the study. No serious adverse events were recorded. The most common adverse event was headache with similar frequencies in the two treatments.


CONCLUSIONS
NXY-059 had no clinically significant effect on the PK of digoxin.
Huledal
Gunilla
G
Clinical Development, AstraZeneca R&D Södertälje, Sweden. gunilla.huledal@astrazeneca.com
Nilsson
Dag
D
Kågedal
Matts
M
Reinholdsson
Ingalill
I
Cheng
Yi-Fang
YF
Svensson
Hanna
H
Borgå
Olof
O
van Hout
Mischa
M
D000293:Adolescent; D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D001557:Benzenesulfonates / Q000008:administration & dosage* / Q000097:blood / Q000652:urine; D002853:Chromatography, Liquid / Q000379:methods; D004077:Digoxin / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000097:blood / Q000652:urine
D000889:Anti-Arrhythmia Agents; D001557:Benzenesulfonates; D018696:Neuroprotective Agents; D004077:Digoxin; C120851:disufenton sodium