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Argatroban is Capable of Passing Through the Blood Brain Barrier. Potential Implications in the Management of Thrombotic Stroke
Author(s) -
Fareed Jawed,
Hoppensteadt Debra,
Maddineni Jyothi,
Kaiser Brigitte,
Bacher Peter,
Walenga Jeanine M.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a397-a
Subject(s) - argatroban , medicine , pharmacology , hirudin , anesthesia , dosing , thrombin , platelet
Argatroban is distinct from other direct thrombin inhibitors such as hirudin and bivalirudin in that it is capable of cellular modulation through the regulation of nitric oxide. Argatroban was administered intravenously and subcutaneously to groups of rats (n=8) in bridged dosages of 250 and 500 μg/kg. Blood samples were drawn 30 and 60 minutes and the animals were sacrificed at 120 minutes. Additional studies were carried out with 1 week repeated administration of argatroban. Argatroban levels measured in the blood, urine and spinal fluid by liquid chromatographic methods were proportionate to dosage. The area under the curve for the circulating levels of argatroban was 1.2 – 2.4 fold higher following subcutaneous administration. The amount of argatroban found in the animals administered with repeated doses was higher than that measured in the singly dosed animals. The levels in the animals treated with repeated administration and bridged dosing showed some staircasing effects that were not significant. Analysis of the brain tissue confirmed the presence of argatroban, though this was not dose dependent in the acute studies. These studies clearly show that argatroban can pass through the blood brain barrier and can be detected in the spinal fluid. These observations suggest that argatroban may produce some of its pharmacologic effects at the neuronal level. The beneficial effects of argatroban may be related to central effects which may be independent of its antithrombin actions.