Pharmacokinetics in renally impaired subjects of NXY-059, a nitrone-based, free-radical trapping agent developed for the treatment of acute stroke.
In: European Journal of Clinical Pharmacology, Jg. 58 (2002-09-01), Heft 6, S. 409-415
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Zugriff:
Objective. NXY-059 is a nitrone-based, free-radical trapping agent being developed for the treatment of acute ischaemic stroke. Elimination of NXY-059 is primarily renal. The objective of the study was to investigate the pharmacokinetics of NXY-059 in subjects with renal impairment. Methods. Twenty-four subjects with a glomerular filtration rate (GFR) ranging from 19 ml/min to 100 ml/min received NXY-059 intravenously over a 24-h period. Drug in plasma and urine was measured for 72 h. One-hour loading infusion rates were proportional to body weight, while maintenance infusion rates were proportional to GFR. Target plasma levels were 60 µmol/l for subjects with mild (GFR 50–100 ml/min) and moderate (GFR 30–49 ml/min) renal impairment, and 30 µmol/l for subjects with severe renal impairment (GFR <30 ml/min). GFR was measured as sinistrin clearance. Results. The data indicated no tolerability or safety concerns with NXY-059. The half-life, which normally is approximately 2–4 h, was in the order of 10–12 h in subjects with moderate and severe renal impairment. The distribution parameters steady-state volume of distribution (V ss ) and unbound fraction in plasma at 13–15 l and 0.53–0.58, respectively, were virtually the same as previously observed in healthy subjects. Plasma clearance of NXY-059, which ranged from 9 ml/min to 76 ml/min, was directly proportional to kidney function (GFR) with no discernible contribution by non-renal clearance. The correlation coefficient squared (r 2 ) was 0.93, both when the renal function parameter was GFR and when it was creatinine clearance estimated from serum creatinine, age, weight and sex. Conclusion. Non-renal elimination of NXY-059 appeared to be insignificant even in subjects with low renal capacity. Patients with renal impairment should have their dose of NXY-059 adjusted for renal function, conveniently assessed from serum creatinine. [ABSTRACT FROM AUTHOR]
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Titel: |
Pharmacokinetics in renally impaired subjects of NXY-059, a nitrone-based, free-radical trapping agent developed for the treatment of acute stroke.
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Autor/in / Beteiligte Person: | Strid, Stig ; Borgå, Olof ; Edenius, Charlotte ; Jostell, Karl-Gustav ; Odergren, Tomas ; Weil, Angelika |
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Zeitschrift: | European Journal of Clinical Pharmacology, Jg. 58 (2002-09-01), Heft 6, S. 409-415 |
Veröffentlichung: | 2002 |
Medientyp: | academicJournal |
ISSN: | 0031-6970 (print) |
DOI: | 10.1007/s00228-002-0478-x |
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