Pharmacokinetic simulation of fatal carbamazepine intoxication in 23-month old child following phenytoin discontinuation.
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.
School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, The State University of New York, 202 Kapoor Hall, Buffalo, NY 14214, USA. jvenci3@gmail.com
Jineane V
JV
Venci
Meghan M
MM
Rowcliffe
Lance
L
Wollenberg
Michelle M
MM
Rainka
Fran M
FM
Gengo
D000927:Anticonvulsants / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000506:poisoning; D001344:Autopsy; D001711:Biotransformation; D002220:Carbamazepine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000506:poisoning; D003198:Computer Simulation; D004334:Drug Administration Schedule; D004347:Drug Interactions; D016903:Drug Monitoring; D062787:Drug Overdose / Q000175:diagnosis / Q000209:etiology / Q000473:pathology; D004359:Drug Therapy, Combination; D017809:Fatal Outcome; D053593:Forensic Toxicology; D006801:Humans; D007223:Infant; D008297:Male; D008954:Models, Biological; D009010:Monte Carlo Method; D010672:Phenytoin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D011041:Poisoning / Q000175:diagnosis / Q000209:etiology / Q000473:pathology; D012640:Seizures / Q000188:drug therapy*
D000927:Anticonvulsants; D002220:Carbamazepine; D010672:Phenytoin