Pharmacokinetic simulation of fatal carbamazepine intoxication in 23-month old child following phenytoin discontinuation

• Published in: Forensic science, medicine, and pathology Vol. 9; no. 1; pp. 73 - 76
• Main Authors: Venci, Jineane V., Rowcliffe, Meghan M., Wollenberg, Lance, Rainka, Michelle M., Gengo, Fran M.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.03.2013; Springer
• Subjects: Anticonvulsants - administration & dosage; Anticonvulsants - blood; Anticonvulsants - pharmacokinetics; Anticonvulsants - poisoning; Autopsy; Biotransformation; Carbamazepine; Carbamazepine - administration & dosage; Carbamazepine - blood; Carbamazepine - pharmacokinetics; Carbamazepine - poisoning; Case Report; Computer Simulation; Criminology and Criminal Justice; Drug Administration Schedule; Drug Interactions; Drug Monitoring; Drug Overdose - diagnosis; Drug Overdose - etiology; Drug Overdose - pathology; Drug Therapy, Combination; Drugs; Fatal Outcome; Forensic Medicine; Forensic Toxicology; Humans; Infant; Male; Medical colleges; Medicine; Medicine & Public Health; Models, Biological; Monte Carlo Method; Overdose; Pathology; Phenytoin; Phenytoin - administration & dosage; Phenytoin - blood; Phenytoin - pharmacokinetics; Physiological aspects; Poisoning - diagnosis; Poisoning - etiology; Poisoning - pathology; Seizures - drug therapy; Toxicology; Intoxication; Forensics; Pharmacokinetics; Carbamazepine; Phenytoin
• ISSN: 1547-769X; 1556-2891; 1556-2891
• DOI: 10.1007/s12024-012-9373-7

The antiepileptic, carbamazepine, is extensively metabolized via hepatic enzymes in the cytochrome P450 family and is therefore subject to a myriad of drug interactions. Concomitant administration with phenytoin enhances carbamazepine metabolism thus reducing serum concentrations and necessitating the use of a higher maintenance dose. Removal of phenytoin therapy in the absence of anticipatory dose adjustments and careful monitoring of serum concentrations may result in catastrophic outcomes. Reported herein are the events leading to the death of a 23-month old child who suffered a fatal carbamazepine overdose following withdrawal of phenytoin therapy.