Bromadiolone toxicokinetics: diagnosis and treatment implications.
BACKGROUND
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.


METHODS
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.
Lo
Vanessa M H
VM
Hospital Authority Toxicology Reference Laboratory, Princess Margaret Hospital, Hong Kong, Special Administrative Region, China.
Ching
C K
CK
Chan
Albert Y W
AY
Mak
Tony W L
TW
D015110:4-Hydroxycoumarins / Q000097:blood / Q000493:pharmacokinetics* / Q000506:poisoning*; D000328:Adult; D000925:Anticoagulants / Q000097:blood / Q000493:pharmacokinetics* / Q000506:poisoning*; D000933:Antifibrinolytic Agents / Q000008:administration & dosage; D001777:Blood Coagulation / Q000187:drug effects; D001780:Blood Coagulation Tests; D002853:Chromatography, Liquid; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D062787:Drug Overdose / Q000097:blood / Q000175:diagnosis; D005260:Female; D006207:Half-Life; D006801:Humans; D008954:Models, Biological; D012378:Rodenticides / Q000097:blood / Q000493:pharmacokinetics* / Q000506:poisoning*; D021241:Spectrometry, Mass, Electrospray Ionization; D013406:Suicide, Attempted; D053719:Tandem Mass Spectrometry; D010837:Vitamin K 1 / Q000008:administration & dosage
D015110:4-Hydroxycoumarins; D000925:Anticoagulants; D000933:Antifibrinolytic Agents; D012378:Rodenticides; D010837:Vitamin K 1; C021636:bromadiolone