Monitoring of clozapine and norclozapine plasma concentration-time curves in acute overdose.
METHODS
A 40-year-old schizophrenic man was found unconscious, with constricted pupils, sinus tachycardia, and twitching of the limbs. There were signs of lung infection, which was treated with antibiotics, and mild rhabdomyolysis. He regained consciousness over 8 hours, and reported taking 3-4 g clozapine. Recovery was uneventful. Measured peak clozapine and norclozapine concentrations were 3.53 mg/L and 0.70 mg/L, respectively. The concentration-time curves were biphasic, with secondary peaks at approximately 36 hours postadmission. Terminal elimination half-lives were 16.9 hours and 22.5 hours for clozapine and norclozapine, respectively.


CONCLUSIONS
Clozapine and its metabolite norclozapine can show biphasic plasma concentration-time curves after overdosage.
Renwick
A C
AC
City Hospital Birmingham, United Kingdom.
Renwick
A G
AG
Flanagan
R J
RJ
Ferner
R E
RE
D000208:Acute Disease; D000328:Adult; D014150:Antipsychotic Agents / Q000493:pharmacokinetics / Q000506:poisoning*; D002851:Chromatography, High Pressure Liquid; D003024:Clozapine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000506:poisoning*; D062787:Drug Overdose / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D008297:Male
D014150:Antipsychotic Agents; C058272:norclozapine; D003024:Clozapine