Disposition of dothiepin after overdose: effects of repeated-dose activated charcoal.
Although the tricyclic antidepressant dothiepin is often encountered in deliberate self-poisonings, there are no published studies of its disposition in overdose. In the present study, we have documented the plasma disposition of dothiepin and its major metabolites in eight overdose patients. All had high initial levels of dothiepin (819-3,851 micrograms/L), dothiepin-S-oxide (655-2,162 micrograms/L), nordothiepin (88-422 micrograms/L), and nordothiepin-S-oxide (176-530 micrograms/L) that were considerably above steady-state therapeutic concentrations. In three patients who received treatment with repeated-dose activated charcoal, dothiepin half-lives were 10.6, 12.5, and 13.1 h compared with the literature range of 18.5-24 h. All patients survived and none experienced any significant cardiovascular event despite exhibiting clinical signs of tricyclic antidepressant overdose. We suggest that repeated-dose activated charcoal treatment may decrease the dothiepin half-life after overdose.
Ilett
K F
KF
Department of Pharmacology, University of Western Australia, Nedlands.
Hackett
L P
LP
Dusci
L J
LJ
Paterson
J W
JW
D000328:Adult; D002606:Charcoal / Q000494:pharmacology / Q000627:therapeutic use; D004308:Dothiepin / Q000097:blood / Q000493:pharmacokinetics* / Q000506:poisoning; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D011041:Poisoning / Q000188:drug therapy / Q000378:metabolism*; D014018:Tissue Distribution
D002606:Charcoal; D004308:Dothiepin