Pharmacokinetics and pharmacodynamics of quetiapine in a patient with a massive overdose.
We present a case of massive overdose with the atypical antipsychotic quetiapine in a 34-year-old woman (body weight 65 kg). At admission, approximately 2 to 4 hours after ingestion of approximately 24 g of quetiapine, the patient was comatose (Glasgow Coma Scale score 5), requiring orotracheal intubation and transfer to the intensive care unit. Because of myoclonic jerks and generalized seizures, benzodiazepines were administered. In addition to transient mild hypotension after intubation, the main cardiovascular manifestation was sinus tachycardia. The QT interval was normal, and the QTc interval (Bazett's correction) was maximally prolonged to 620 ms. However, no malignant arrhythmias were observed. The patient recovered within 2 days but remained agitated and aggressive, for which she was transferred to the psychiatric clinic. The pharmacokinetics of quetiapine in such a large overdose could not be described by simple first-order kinetics. The initially observed rapid decline of the plasma concentrations of quetiapine could be simulated by first-order kinetics (half life = 4.1 hr) and can most probably be explained by rapid distribution into tissues. The final elimination of the drug from the body occurred after approximately 34 hours at much slower rate, most probably reflecting redistribution from tissues into blood and consecutive hepatic clearance of the drug.
Bodmer
Michael
M
Department of Clinical Pharmacology and Toxicology, University Hospital Basel, Basel, Switzerland. BodmerM@uhbs.ch
Burkard
Thilo
T
Kummer
Oliver
O
Beyrau
Ralf
R
Krähenbühl
Stephan
S
Haschke
Manuel
M
D000328:Adult; D014150:Antipsychotic Agents / Q000493:pharmacokinetics* / Q000506:poisoning*; D001342:Autonomic Nervous System Diseases / Q000139:chemically induced; D002851:Chromatography, High Pressure Liquid; D003128:Coma / Q000139:chemically induced; D003865:Major Depressive Disorder / Q000150:complications; D003987:Dibenzothiazepines / Q000493:pharmacokinetics* / Q000506:poisoning*; D062787:Drug Overdose; D005260:Female; D015600:Glasgow Coma Scale; D006207:Half-Life; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced; D010275:Parasympathetic Nervous System; D000069348:Quetiapine Fumarate; D012559:Schizophrenia / Q000150:complications; D012640:Seizures / Q000139:chemically induced; D013406:Suicide, Attempted
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate