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PIII‐71
Author(s) -
Reinholdsson I.,
Nilsson D.,
Huledal G.,
Åsenblad N.,
Cheng Y.,
Kågedal M.,
Borgå O.
Publication year - 2006
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2005.12.279
Subject(s) - cefuroxime , placebo , medicine , urine , pharmacology , stroke (engine) , anesthesia , chemistry , antibiotics , pathology , mechanical engineering , biochemistry , alternative medicine , engineering
BACKGROUND NXY‐059 is a novel, free‐radical trapping neuroprotectant that reduces infarct size and preserves brain function in animal models of acute ischemic stroke (AIS). In an initial Phase III study (SAINT I) NXY‐059 has shown efficacy in AIS by reducing functional disability. Approximately 30% of NXY‐059 is eliminated by active tubular secretion by an organic anion transporter (OAT) in the kidneys. Cefuroxime is eliminated renally, partially (45%) by OAT. This study explored whether co‐administration of cefuroxime reduced the elimination of NXY‐059, and vice versa. METHODS This was an open, single‐center, randomized, three‐period, crossover study. Twenty‐three healthy subjects completed the study. NXY‐059 / placebo was infused over 10h. Doses were similar to those used in the Phase III program. A clinically recommended cefuroxime dose (1.5g iv), or placebo, was infused over 30 min, 4h after the start of the NXY‐059 / placebo infusion. Blood and urine were collected for 10h for determination of NXY‐059 and cefuroxime. RESULTS NXY‐059 reduced the renal clearance (CL R ) of cefuroxime by 27% (p<0.001) causing the area under the concentration‐time curve of cefuroxime to increase by 27%. There was no evidence of any effect of cefuroxime on the CL R of NXY‐059. No safety concerns were raised. CONCLUSIONS NXY‐059 reduced the elimination of cefuroxime due to competitive inhibition of OAT. The reduction is limited in relation to the wide therapeutic window of cefuroxime and thus of no clinical significance. Clinical Pharmacology & Therapeutics (2005) 79 , P78–P78; doi: 10.1016/j.clpt.2005.12.279