Effect of NXY-059, a novel neuroprotectant, on the pharmacokinetics of a single dose of digoxin in healthy subjects

ABSTRACT

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.

Research design and 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.

Main outcome measures: 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.

Key words: :

• Acute ischaemic stroke
• Digoxin
• NXY-059
• Pharmacokinetics
• Renal excretion