Bromadiolone toxicokinetics: Diagnosis and treatment implications

Introduction. Ingestion of bromadiolone can lead to prolonged and life-threatening coagulopathy. Traditional treatment of bromadiolone intoxication relies on the coagulation profile. Currently, there is scanty information on bromadiolone elimination kinetics and half-life. Case Report. We report a c...

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Published in:	Clinical toxicology (Philadelphia, Pa.) Vol. 46; no. 8; pp. 703 - 710
Main Authors:	Lo, Vanessa Mh, Ching, Ck, Chan, Albert Y.W., Mak, Tony W.L.
Format:	Journal Article
Language:	English
Published:	Philadelphia, PA Informa UK Ltd 01-09-2008 Taylor & Francis
Subjects:	4-Hydroxycoumarins - blood 4-Hydroxycoumarins - pharmacokinetics 4-Hydroxycoumarins - poisoning Adult Anticoagulants - blood Anticoagulants - pharmacokinetics Anticoagulants - poisoning Antifibrinolytic Agents - administration & dosage Biological and medical sciences Blood Coagulation - drug effects Blood Coagulation Tests Chromatography, Liquid Coagulopathy Drug Administration Schedule Drug intoxications. Doping Drug Monitoring Drug Overdose - blood Drug Overdose - diagnosis Female Half life Hematologic and hematopoietic diseases Humans Medical sciences Models, Biological Pharmacology. Drug treatments Platelet diseases and coagulopathies Poisoning management Rodenticides - blood Rodenticides - pharmacokinetics Rodenticides - poisoning Spectrometry, Mass, Electrospray Ionization Suicide, Attempted Tandem Mass Spectrometry Toxicokinetics Vitamin K 1 - administration & dosage Human Toxicokinetics Poisoning management Clinical management Treatment Drug intoxication Hemopathy Diagnosis Coagulopathy Half life
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Summary:	Introduction. Ingestion of bromadiolone can lead to prolonged and life-threatening coagulopathy. Traditional treatment of bromadiolone intoxication relies on the coagulation profile. Currently, there is scanty information on bromadiolone elimination kinetics and half-life. Case Report. We report a case of bromadiolone poisoning in a 40-year old female who, by history, ingested four 42.5-gram bags of rat poison (0.005% bromadiolone), equivalent to 8.5 mg bromadiolone (0.17 mg kg body weight), four days prior to admission. On admission, her prothrombin time was 92.0 seconds, international normalized ratio was 5.7, and activated partial thromboplastin time was 50.2 seconds with no bleeding on clinical examination. The first plasma bromadiolone level (5 days post-ingestion) was 92 ng mL. Serial measurement of plasma bromadiolone levels confirmed the diagnosis and demonstrated that bromadiolone obeys the elimination kinetic of a two-compartment model with a rapid, fairly steep decline phase (half-life 3.5 days) followed by a slower termination phase (half-life 24 days). Plasma bromadiolone level of less than 10 ng mL in our patient was associated with a consistently normal coagulation profile without vitamin K1 therapy. Conclusions. There is a lack of information on the toxicodynamics and toxicokinetics of bromadiolone in humans; further studies are needed before the plasma bromadiolone level can serve as one of the logical and safe therapeutic endpoints for vitamin K1 therapy.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1556-3650 1556-9519
DOI:	10.1080/15563650701504366