vitamin-k-1 and chlorophacinone

A 33-year-old man was admitted 8 hours after voluntary ingestion of 1875 mg of chlorophacinone (C'Operat 750 mL). The examination revealed excitation and nausea, with a normal prothrombin index (PI). Comprehensive testing for abused and therapeutic drugs in blood confirmed chlorophacinone (maximum plasma level: 27.6 mg/L), an antivitamin K (AVK) rodenticide. In a search for easy toxicological management of chlorophacinone poisoning treated by phytomenadione and a cytochrome P450 inducer (phenobarbital), PI and chlorophacinone plasma levels were monitored concomitantly during 17 days. A simple HPLC procedure for the determination of chlorophacinone in human plasma is reported for that purpose. Under phenobarbital 200 mg/day, chlorophacinone exhibited an apparent elimination half-life (3.27 days) shorter than in previously reported cases. If PI is useful for planning phytomenadione treatment and used for therapeutic monitoring of AVK, the chlorophacinone concentrations follow-up may provide a better estimation of the duration of hospitalisation. Chlorophacinone accumulation in target cells or existence of an unidentified metabolite may explain persistence of the hypocoagulability syndrome at low plasmatic concentrations of chlorophacinone. This case illustrates how toxicological management may facilitate toxicokinetics and therapeutic data acquisition.

Topics: Adult; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Tests; Chromatography, High Pressure Liquid; Drug Monitoring; Drug Overdose; Emergency Treatment; Humans; Indans; Male; Substance Abuse Detection; Suicide, Attempted; Vitamin K 1

Plasma chlorophacinone determinations were performed in three cases of intoxication. The data collected in this study confirm the particularly prolonged anticoagulant effect of this compound and show that the knowledge of plasma concentrations may be very useful for clinicians since it allows to confirm the diagnosis and to evaluate the duration of the treatment. The determination of half-lives was investigated and the results indicate that the greater the quantity absorbed, the longer the half-life. The effect of phenobarbital on the elimination of cholorophacinone could be studied in one case. An increased elimination was noted when phenobarbital was administered.

Topics: Adult; Chromatography, High Pressure Liquid; Female; Humans; Indans; Indenes; Male; Middle Aged; Phenobarbital; Rodenticides; Vitamin K 1